|
Rat small intestine is an
insulin-sensitive gluconeogenic organ.
Croset M, Rajas F, Zitoun C, Hurot JM, Montano S,
Mithieux G. Institut National de la Sante et de la
Recherche Medicale, Faculte de Medecine RTH Laennec, Lyon,
France.
Diabetes 2001 Apr;50(4):740-6
At variance with the current view that only liver and
kidney are gluconeogenic organs, because both are the only
tissues to express glucose-6-phosphatase (Glc6Pase), we
have recently demonstrated that the Glc6Pase gene is
expressed in the small intestine in rats and humans and
that it is induced in insulinopenic states such as fasting
and diabetes. We used a combination of arteriovenous
balance and isotopic techniques, reverse
transcription-polymerase chain reaction, Northern blot
analysis, and enzymatic activity assays. We report that rat
small intestine can release neosynthesized glucose in
mesenteric blood in insulinopenia, contributing 20-25% of
total endogenous glucose production. Like liver glucose
production, small intestine glucose production is acutely
suppressed by insulin infusion. In the small intestine,
glutamine and, to a much lesser extent, glycerol are the
precursors of glucose, whereas alanine and lactate are the
main precursors in liver. Accounting for these metabolic
fluxes: 1) the phosphoenolpyruvate carboxykinase gene
(required for the utilization of glutamine) is strongly
induced at the mRNA and enzyme levels in insulinopenia; 2)
the glycerokinase gene is expressed, but not induced; 3)
the pyruvate carboxylase gene (required for the utilization
of alanine and lactate) is repressed by 80% at the enzyme
level in insulinopenia. These studies identify small
intestine as a new insulin-sensitive tissue and a third
gluconeogenic organ, possibly involved in the
pathophysiology of diabetes.
Protective effects of
pyridoxal phosphate against glucosedeprivation- induced
damage in cultured hippocampal neurons
Geng M.-Y.; Saito H.; Nishiyama N. Dr. N. Nishiyama,
Department of Chemical Pharmacology, Faculty of
Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113 Japan
Journal of Neurochemistry (USA), 1997, 68/6
(2500-2506)
When hippocampal cultures were deprived of glucose,
massive release of lactate dehydrogenase (LDH), an
indicator of neuronal death, occurred via NMDA receptor
activation. Addition of pyridoxal phosphate (PLP; 1 and 10
microM) inhibited this LDH release in a
concentration-dependent manner. Prior exposure to PLP
evoked more potent inhibitory effects on LDH release
compared with those treated at the onset of glucose
deprivation. Furthermore, PLP inhibited the reduction of
intracellular content of pyruvate induced by glucose
deprivation, which was accompanied by the reversal of
intracellular ATP depletion. A noteworthy elevation of
extracellular glutamate in response to glucose deprivation
was completely reversed by addition of PLP. Aminooxyacetic
acid, a potent inhibitor of PLP-dependent enzymes,
antagonized the effects of PLP on LDH release, pyruvate
production, and ATP formation. These results suggest that
PLP protects neurons from glucose deprivation- induced
damage by enhancing the formation of energy-yielding
products and relieving extracellular load of glutamate. The
observed phenomena further indicate that PLP might be used
prophylactically against neuronal death induced by
metabolic disorders.
Dietary conjugated
linoleic acid normalizes impaired glucose tolerance in the
Zucker diabetic fatty fa/fa rat.
Houseknecht KL, Vanden Heuvel JP, Moya-Camarena SY,
Portocarrero CP, Peck LW, Nickel KP, Belury MA. Department
of Animal Sciences, Purdue University, West Lafayette,
Indiana 47907, USA.
Biochem Biophys Res Commun 1998 Jun 29;247(3):911
Conjugated linoleic acid (CLA) is a naturally occurring
fatty acid which has anti-carcinogenic and anti-atherogenic
properties. CLA activates PPAR alpha in liver, and shares
functional similarities to ligands of PPAR gamma, the
thiazolidinediones, which are potent insulin sensitizers.
We provide the first evidence that CLA is able to normalize
impaired glucose tolerance and improve hyperinsulinemia in
the pre-diabetic ZDF rat. Additionally, dietary CLA
increased steady state levels of aP2 mRNA in adipose tissue
of fatty ZDF rats compared to controls, consistent with
activation of PPAR gamma. The insulin sensitizing effects
of CLA are due, at least in part, to activation of PPAR
gamma since increasing levels of CLA induced a
dose-dependent transactivation of PPAR gamma in CV-1 cells
cotransfected with PPAR gamma and PPRE X 3-luciferase
reporter construct. CLA effects on glucose tolerance and
glucose homeostasis indicate that dietary CLA may prove to
be an important therapy for the prevention and treatment of
NIDDM.
Chromium and other
insulin sensitizers may enhance glucagon secretion:
Implications for hypoglycemia and weight
control
McCarty M.F. Nutrition 21, Suite 335, 1010 Turquoise
Street, San Diego, CA 92109 USA
Medical Hypotheses (United Kingdom), 1996, 46/2
(77-80)
Increased pancreatic beta-cell secretory activity
usually is associated with decreased alpha-cell activity;
stimulated beta-cells release gamma-aminobutyric acid,
which hyperpolarizes alpha-cells, inhibiting glucagon
release. Thus, insulin secretion and glucagons secretion
are usually inversely coupled. This suggests that chromium
and other insulin-sensitizing modalities, by
down-regulating beta-cell activity, may increase glucagons
secretion. Such an effect might play a role in the
documented therapeutic activity of supplemental chromium
and biguanides in reactive hypoglycemia, and might also be
of benefit to dieters.
New data and concepts on
glutamine and glucose metabolism in the gut.
Mithieux G. INSERM U. 449, Faculte de Medecine R.T.H.
Laennec, rue Guillaume Paradin, F69372 Lyon Cedex 08,
France. mithieux@laennec.univ-lyon1.fr
Curr Opin Clin Nutr Metab Care 2001 Jul;4(4):267-71
Both glutamine and glucose are highly utilized by the
small intestine in various animal species. They are,
however, very partially oxidized, the major known fate of
glucose being lactate and alanine, and that of glutamine
being citrulline or proline. At variance with the current
view that only the liver and kidney are gluconeogenic
organs, because both are the only tissues to express the
glucose-6 phosphatase gene, this gene is also expressed in
the small intestine in rats and humans, and is strongly
induced in insulinopenic states, such as fasting and
diabetes. Under the latter conditions, the small intestine
contributes 20-25% of whole-body endogenous glucose
production. The main small intestine gluconeogenic
substrate is glutamine and, to a lesser extent, glycerol.
Accounting for these fluxes, the phosphoenolpyruvate
carboxykinase gene is strongly induced in insulinopenia
and, although up to now it had been considered absent from
this tissue, the glycerokinase gene is expressed in the
small intestine. The production of glucose by the small
intestine may be acutely blunted upon insulin infusion.
These new data also emphasize the central role of alanine
aminotransferase in the coupling of glutamine and glucose
metabolisms in the small intestine.
Preventing
Hypoglycemia
Durk Pearson and Sandy Shaw
Anti-Aging News, January 1982 Vo.2, No. 1 pg 6-7
Cysteine is a strong reducing agent (it can prevent
oxidation of some other substances). In fact, it has been
found that too much cysteine in a cell culture medium can
inactivate the hormone insulin contained in the medium. The
insulin molecule contains three disulfide bonds, at least
one of which can be reduced by cysteine. When this happens,
the insulin molecule can no longer maintain the proper
shape to function normally in stimulating the metabolism of
sugar. In hypoglycemia attacks, there is too much insulin
and too little sugar in the blood stream. Cysteine can
inactivate insulin, thereby allowing the sugar level to
begin to rise again. We and others have used the
combination of vitamins B1, C, and cysteine to successfully
abort severe attacks of hypoglycemia. A reasonable dose for
a healthy adult is 5 grams of C, 1 gram of B1, and 1 gram
cysteine. Although cysteine is a nutrient, it s use on a
long-term basis should be considered experimental. Start
with a low dose (250 milligrams per day) and work your way
up. Always use at least three times as much Vitamin-C as
cysteine. Be sure to consult with your physician and have
regular clinical tests of basic body functions, especially
liver and kidney. Diabetics should not use cysteine
supplements due to its anti-insulin effects.
Isomer-specific
antidiabetic properties of conjugated linoleic acid.
Improved glucose tolerance, skeletal muscle insulin action,
and UCP-2 gene expression.
Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M,
Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron
MJ, Zierath JR, Houseknecht KL. Department of Clinical
Physiology, Karolinska Institute, Stockholm, Sweden.
Diabetes 2001 May;50(5):1149-57
Conjugated linoleic acid (CLA) isomers have a number of
beneficial health effects, as shown in biomedical studies
with animal models. Previously, we reported that a mixture
of CLA isomers improved glucose tolerance in ZDF rats and
activated peroxisome proliferator-activated receptor
(PPAR)-gamma response elements in vitro. Here, our aim was
to elucidate the effect(s) of specific CLA isomers on
whole-body glucose tolerance, insulin action in skeletal
muscle, and expression of genes important in glucose and
lipid metabolism. ZDF rats were fed either a control diet
(CON), one of two CLA supplemented diets (1.5% CLA)
containing differing isoforms of CLA (47% c9,t11; 47.9%
c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were
pair-fed CON diet to match the intake of 50:50. The 50:50
diet reduced adiposity and improved glucose tolerance
compared with all other ZDF treatments. Insulin-stimulated
glucose transport and glycogen synthase activity in
skeletal muscle were improved with 50:50 compared with all
other treatments. Neither phosphatidlyinositol 3-kinase
activity nor Akt activity in muscle was affected by
treatment. Uncoupling protein 2 in muscle and adipose
tissue was upregulated by c9,t11 and 50:50 compared with
ZDF controls. PPAR-gamma mRNA was downregulated in liver of
c9,t11 and pair-fed ZDF rats. Thus, the improved glucose
tolerance in 50:50 rats is attributable to, at least in
part, improved insulin action in muscle, and CLA effects
cannot be explained simply by reduced food intake.
Role of glutamine in
human carbohydrate metabolism in kidney and other
tissues.
Stumvoll M, Perriello G, Meyer C, Gerich J. Medizinische
Klinik, Eberhard-Karls-Universitat, Tubingen, Germany.
Kidney Int 1999 Mar;55(3):778-92
Glutamine is the most abundant amino acid in the human
body and is involved in more metabolic processes than any
other amino acid. Until recently, the understanding of many
aspects of glutamine metabolism was based on animal and in
vitro data. However, recent studies using isotopic and
balance techniques have greatly advanced the understanding
of glutamine metabolism in humans and its role in glucose
metabolism in the kidney and other tissues. There is now
evidence that in postabsorptive humans, glutamine is an
important glucose precursor and makes a significant
contribution to the addition of new carbon to the glucose
carbon pool. The importance of alanine for gluconeogenesis,
viewed in terms of the addition of new carbons, is less
than previously assumed. It appears that glutamine is
predominantly a renal gluconeogenic substrate, whereas
alanine gluconeogenesis is essentially confined to the
liver. As shown recently, renal gluconeogenesis contributes
20 to 25% to whole-body glucose production. Moreover,
glutamine has been shown not only to stimulate net muscle
glycogen storage but also to stimulate gluconeogenesis in
normal humans. Finally, in humans with type II diabetes,
conversion of glutamine to glucose is increased (more so
than that of alanine). The available evidence on the
hormonal regulation of glutamine gluconeogenesis in kidney
and liver and its alterations under pathological conditions
are discussed.
SUGGESTED
READING
Renal substrate
metabolism and gluconeogenesis during hypoglycemia in
humans.
Cersosimo E, Garlick P, Ferretti J. Department of
Medicine, State University of New York at Stony Brook,
11794-8154, USA. ecersosi@mail.som.sunysb.edu
Diabetes 2000 Jul;49(7):1186-93
To examine the potential contribution of precursor
substrates to renal gluconeogenesis during hypoglycemia, 14
healthy subjects had arterialized hand vein and renal vein
(under fluoroscopy) catheterized after an overnight fast.
Net renal balance of lactate, glycerol, alanine, and
glutamine was determined simultaneously with systemic and
renal glucose kinetics using arteriovenous concentration
differences and 6-[2H2]glucose tracer dilution. Renal
plasma flow was measured by para-aminohippurate clearance
and was converted to blood flow using the mathematical
value (1-hematocrit). Arterial and renal vein samples were
obtained in the postabsorptive state and during a 180-min
hyperinsulinemic period during either euglycemia or
hypoglycemia. Insulin increased from 49 +/- 14 to 130 +/-
25 pmol/l (hypoglycemia) and to 102 +/- 10 pmol/l
(euglycemia). Arterial blood glucose decreased from 4.5
+/-0.2 to 3.0 +/- 0.1 mmol/l during hypoglycemia but did
not change during euglycemia (4.3 +/- 0.2 mmol/l). After
150 min, endogenous glucose production reached a plateau
value that was higher during hypoglycemia (10.3 +/0.6
micromol x kg(-1) x min(-1)) than during euglycemia (5.73
+/-0.6 micromol x kg(-1) x min(-1), P < 0.001).
Hypoglycemia was associated with a rise in renal glucose
production (RGP) from 3.0 +/- 0.7 to 5.4 +/- 0.6 micromol x
kg(-1) x min(-1) (P < 0.05), although glucose
utilization remained the same (2.0 +/- 0.8 vs. 2.1 +/-0.6
micromol x kg(-1) x min(-1)). As a result, net renal
glucose output increased from 1.0 +/- 0.3 to 3.3 +/- 0.40
micromol x kg(-1) x min(-1). Elevations in net renal uptake
of lactate (2.4 +/- 0.5 to 3.5 +/- 0.7 vs. 2.8 +/- 0.4
micromol x kg(-1) x min(-1)), glycerol (0.6 +/- 0.3 to 1.3
+/- 0.5 vs. 0.4 +/- 0.2 micromol x kg(-1) x min(-1)), and
glutamine (0.7 +/- 0.2 to 1.1 +/- 0.3 vs. 0.1 +/- 0.3
micromol x kg(-1) x min(-1)) during hypoglycemia versus
euglycemia (P < 0.05) could account for nearly 60%
of all glucose carbons released in the renal vein during
hypoglycemia. Our data indicate that extraction of
circulating gluconeogenic precursors by the kidney is
enhanced and responsible for a substantial fraction of the
compensatory rise in RGP during sustained hypoglycemia.
Increased renal gluconeogenesis from circulating substrates
represents an additional physiological mechanism by which
the decrease in blood glucose concentration is attenuated
in humans.
Renal glucose
production during insulin-induced hypoglycemia in
humans.
Cersosimo E, Garlick P, Ferretti J. Department of
Medicine, State University of New York at Stony Brook,
11794-8154, USA. ecersosi@mail.som.sunysb.edu
Diabetes 1999 Feb;48(2):261-6
We investigated the effects of hypoglycemia on renal
glucose production (RGP) and renal glucose uptake (RGU)
using arteriovenous balance combined with tracer technique
in humans. Our 14 healthy subjects had arterialized hand
veins (artery) and renal veins (under fluoroscopy)
catheterized after an overnight fast. Systemic and renal
glucose kinetics were measured with infusion of
[6-(2)H2]glucose, and renal plasma flow was measured by
para-aminohippurate clearance. After a 150-min
equilibration period, artery and renal vein samples were
obtained between -30 and 0 min, and subjects received a
180-min peripheral insulin infusion (0.250 mU kg(-1) x
min(-1)) with a variable infusion of [6-(2)H2]dextrose
adjusted to maintain plasma glucose at either approximately
60 mg/dl (hypoglycemic clamp) or approximately 90 mg/dl
(euglycemic clamp). Blood samples were obtained between 150
and 180 min during the study period. Insulin increased from
49 +/- 14 to 130 +/- 25 (hypoglycemia) and to 102 +/- 10
(euglycemia) pmol/l. Glucose decreased from 5.32 +/- 0.11
to 3.58 +/- 0.07 micromol/ml during hypoglycemia, but it
did not change during euglycemia (5.20 +/- 0.19 vs. 5.05
+/- 0.15 micromol/ml). Endogenous glucose production
decreased (9.30 +/- 0.70 vs. 5.65 +/- 0.50) during
euglycemia but not during hypoglycemia (9.80 +/- 0.50 vs.
10.25 +/- 0.60 micromol x kg(-1) x min(-1)). During
hypoglycemia, net renal glucose output increased from 0.54
+/- 0.30 to 2.31 +/- 0.40, RGP increased from 1.88 +/- 0.70
to 3.65 +/- 0.50 (P < 0.05), and RGU did not change
(1.34 +/- 0.50 vs. 1.34 +/- 0.60 micromol x kg(-1) x
min(-1)). During euglycemia, renal glucose balance switched
from a net output of 0.72 +/- 0.20 to a net uptake of 1.70
+/- 0.92, RGP decreased from 2.31 +/- 0.50 to 1.20 +/-
0.58, and RGU increased from 1.59 +/- 0.50 to 2.90 +/- 0.70
micromol x kg(-1) x min(-1) (P < 0.05). During
hypoglycemia, arterial glucagons increased from 105 +/- 6
to 129 +/- 8, epinephrine increased from 116 +/- 28 to 331
+/- 33, norepinephrine increased from 171 +/- 9 to 272 +/-
9 (all P < 0.05), and renal vein norepinephrine
increased from 236 +/- 13 to 426 +/- 50 (P < 0.001).
These data indicate that, in addition to counterregulatory
hormones, activation of the autonomic nervous system during
hypoglycemia stimulates glucose production by the kidney,
which may represent an important additional component of
the body's defense against hypoglycemia in humans.
Oral administration of
growth hormone (GH) releasing peptide-mimetic MK-677
stimulates the GH/insulin-like growth factor-I axis in
selected GH-deficient adults.
Chapman IM; Pescovitz OH; Murphy G; Treep T; Cerchio KA;
Krupa D; Gertz B; Polvino WJ; Skiles EH; Pezzoli SS;
Thorner MO Department of Medicine, University of Virginia,
Charlottesville 22908, USA.
J Clin Endocrinol Metab (United States) Oct 1997, 82
(10) p3455-63
To determine the effect of the GH releasing peptide
(GHRP)-mimetic, MK-677, on the GH/insulin-like growth
factor-I (IGF-I) axis in selected GH-deficient adults, we
studied nine severely GH-deficient men [peak serum GH
concentration in response to insulin-induced hypoglycemia
of 1.2 +/- 1.5 micrograms/L, mean +/- SD (range
0.02-4.79)], age 17-34 yr, height 168 +/- 1.5 cm, body mass
index 22.6 +/- 3.3 kg/m2, who had been treated for GH
deficiency with GH during childhood. In a double-blind
rising-dose design, subjects received once daily oral doses
of 10 or 50 mg MK-677 or placebo for 4 days over two
treatment periods separated by at least 28 days. Four
subjects received placebo and 10 mg/day MK-677 in a
cross-over fashion in periods 1 and 2. Five subjects
received 10 mg and then 50 mg/day MK-677 in a sequential,
rising-dose fashion in periods 1 and 2, respectively. Blood
was collected every 20 min for 24 h before treatment and at
the end of each period for GH measurement using an
ultrasensitive assay. The drug was generally well
tolerated, with no significant changes from baseline in
circulating concentrations of cortisol, PRL, and thyroid
hormones. Serum IGF-i and 24-H mean GH concentrations
increased in all subjects after treatment with both 10 and
50 mg/day MK-677 vs. baseline. After treatment with 10 mg
MK-677, IGF-I concentrations increased 52 +/- 20% (65 +/- 6
to 99 +/- 9 micrograms/L, geometric mean +/- intrasubject
SE, P < or = 0.05 vs. baseline), and 24 h mean GH
concentrations increased 79 +/- 19% (0.14 +/- 0.01 to 0.26
+/- 0.02 microgram/L, P < or = 0.05 vs. baseline).
Following treatment with 50 mg MK-677, IGF-I concentrations
increased 79 +/- 9% (84 +/- 3 to 150 +/- 6 micrograms/L, P
< or = 0.05 vs. baseline) and 24-h mean GH
concentrations increased 82 +/- 29% (0.21 +/- 0.02 to 0.39
+/- 0.04 microgram/L, P < or = 0.05 vs. baseline),
respectively. Serum IGF binding protein-3 concentrations
increased with both 10 mg (1.2 +/- 0.1 to 1.7 +/- 0.1
micrograms/L, P < or = 0.05) and 50 mg MK-677 (1.7
+/- 0.1 to 2.2 +/- 0.2 micrograms/L, P < or = 0.05).
The GH response to MK-677 was greater in subjects who were
the least GH/IGF-I deficient at baseline; by linear
regression analysis the increase in 24-h mean GH
concentration was positively related to both baseline 24-h
mean GH concentration (r = 0.81, P = 0.009) and baseline
IGF-I (r = 0.79, P = 0.01) for 10 mg MK-677. IGF-I
responses were not significantly related to any baseline
measurement. Fasting and postprandial insulin and
postprandial glucose increased significantly after MK-677
treatment, and the clinical significance of these changes
will need to be assessed in longer term studies. Oral
administration of such GHRP-mimetic compounds may have a
role in the treatment of GH deficiency of childhood
onset.
Effect of melatonin on
hypoglycemia and metoclopramide-stimulated arginine
vasopressin secretion in normal men.
Coiro V; Volpi R; Caffarri G; Capretti L; Marchesi C;
Giacalone G; Chiodera P Department of Internal Medicine,
School of Medicine, University of Parma, Italy.
Neuropeptides (Scotland) Aug 1997, 31 (4) p323-6
The present study was performed in order to establish
whether melatonin (MEL) plays a role in the regulation of
arginine vasopressin secretion (AVP) in normal human
subjects. For this purpose, the effects of an oral
administration of 6 or 12 mg MEL on basal and
metoclopramide (MCP)- or hypoglycemia -stimulated AVP
secretion was tested in 18 normal men. MCP was given at a
dose of 20 mg as an intravenous (i.v.) bolus; hypoglycemia
was induced with an i.v. bolus injection of 0.15 IU/kg body
weight of insulin. In addition, in view of the well-known
inhibitory effect of MEL on the growth hormone (GH)
response to hypoglycemia, GH levels were measured during
the insulin tolerance test (ITT), as an independent index
of MEL activity. MEL did not produce any change in AVP
secretory patterns in basal conditions or during the MCP
test. In contrast, the mean peak AVP response to
hypoglycemia was 2.33 times higher than baseline in the
control ITT, whereas it was only 1.77 times higher than
baseline in the ITT plus MEL tests. Also, the GH response
to hypoglycemia was significantly lower in the presence
than in the absence of MEL. For both AVP and GH, the
inhibitory effect of MEL during ITT was similar, when
either 6 or 12 mg MEL was given. These data indicate an
involvement of MEL in the control of the AVP response to
hypoglycemia, but not of basal and MCP-induced AVP
secretion. In addition, the similar effects of MEL on GH
and AVP secretions during ITT suggest that similar
neuroendocrine mechanisms underlie these hormonal responses
to hypoglycemia.
Nutritional strategies
to minimize fatigue during prolonged exercise: fluid,
electrolyte and energy replacement.
Dennis SC; Noakes TD; Hawley JA MRC/UCT Bioenergetics of
Exercise Research Unit, University of Cape Town Medical
School, Sports Science, Institute of South Africa,
Newlands, South Africa.
J Sports Sci (England) Jun 1997, 15 (3) p305-13
While the presence of palatable (20 mmol l-1)
concentrations of NaCl in drinks containing carbohydrate
consumed during intense exercise would not be expected to
promote absorption or significantly help maintain fluid
balance, there is no doubt that athletes should ingest some
from of carbohydrate (other than fructose) during
moderate-intensity exercise lasting > 90 min. As
only approximately 20 g of ingested carbohydrate is
oxidized in the first hour of exercise, athletes should
probably consume 100 ml every 10 min of a dilute (3-5 g 100
ml-1) carbohydrate solution and thereafter increase the
carbohydrate concentration to approximately 10 g 100 ml-1
to match the peak (approximately 1 g min-1) rates of plasma
glucose oxidation. Drinking more than those amounts of
carbohydrate may increase muscle glycogen oxidation by
attenuating the fall in plasma insulin concentration and
thereby delaying fat mobilization, especially at relatively
low (55% of peak oxygen consumption) intensity exercise. As
carbohydrate ingestion does not slow the rate of glycogen
utilization in working muscle, it is also advisable for
endurance athletes to start exercise with an adequate
supply of muscle glycogen, irrespective of whether or not
they ingest carbohydrate during exercise. While
carbohydrate ingestion 'spares' conversion of liver
glycogen to plasma glucose and prevents hypoglycemia, it
does not delay the fatigue associated with a low
(approximately 20 mmol kg-1) glycogen content in working
muscle. Conversely, increases in glycogen content of
working muscle at the start of exercise have no effect on
the rates of plasma glucose oxidation. Higher initial rates
of glycogen utilization by active muscles in
'carbohydrate-loaded' subjects decrease the indirect
oxidation (via lactate) of non-working muscle glycogen,
rather than the conversion of liver glycogen to plasma
glucose. Hence, athletes should ingest carbohydrate during
endurance exercise even if they have 'carbohydrate-loaded'
before exercise.
Effects of coca chewing
on the glucose tolerance test
Galarza Guzman M; Penaloza Imana R; Echalar Afcha L;
Aguilar Valerio M; Spielvogel H; Sauvain M Laboratorio de
Bioquimica, Instituto Boliviano de Biologia de la Altura,
Facultad de Medicina, Universidad Mayor de San Andres,
Orstom, Bolivia.
Medicina (B Aires) (Argentina) 1997, 57 (3) p261-4
The effects of coca chewing on the glucose tolerance
test were measured. The subjects were 14 habitual coca
chewers and 14 non-chewers. All were of Aymara ancestry and
came from a rural community from the "Altiplano" close to
the city of La Paz. The coca users chewed coca leaves
during 3 1/2 hours of the test. The non-chewers showed a
significant hypoglycemia at 120 minutes of the test. This
effect was not observed in the coca chewers. The hormonal
counter-regulation response to hypoglycemia worked
perfectly in non-chewers, since glucose levels reached
normal values at 180 minutes of the test. These results
suggest that coca chewers, at high altitude do not present
hypoglycemia, due to an antagonic action of coca
metabolites on insulin; allowing a greater availability of
glucose in the organism. This would have a positive effect
on metabolism in an environment of hypobaric hypoxia, known
to lead to situations of hypoglycemia.
A metabolic
complications of nutritional support. I. Carbohydrates,
amino acids, fats, water, ions, trace elements
Kazda A. Dr. A. Kazda, Addeleni Klinicke Biochemie, VFN,
I Lekarska Fak., Univ Karlova, Karlovo nam. 32, 121 11
Praha 2 Czech Republic
Klinicka Biochemie a Metabolismus (Czech Republic) 1997,
5/4 (251-257)
The paper discusses the metabolic complications
described in relation to intake of carbohydrates, amino
acids and fats as compounds is parenteral nutrition (PN).
Also, the symptoms of possible deficiencies of these
nutrients during PN are mentioned. Attention is paid to the
dysbalances of selected ions, above all magnesium and
phosphate. The significance of trace elements in
nutritional support is particularly stressed with respect
to metabolism of free radicals. The laboratory monitoring
of zinc, and selenium, clinical signs of their deficiency
and supplementation during PN are presented. Intoxications
described during parenteral supplementation of chromium and
manganese are described.
Metabolic response to
lactitol and xylitol in healthy men.
Natah SS; Hussien KR; Tuominen JA; Koivisto VA Helsinki
University Central Hospital, Department of Medicine,
Finland.
Am J Clin Nutr (United States) Apr 1997, 65 (4)
p947-50
Sugar alcohols are used in food products, yet their
metabolic effects in humans are poorly known. We examined
plasma glucose, insulin, and C-peptide responses and
changes in carbohydrate and lipid oxidation after the
ingestion of 25 g lactitol, xylitol, or glucose. Eight
healthy, nonobese men were studied after an overnight fast.
After the ingestion of lactitol or xylitol, the rise in
plasma glucose, insulin, and C-peptide concentrations was
less than after the ingestion of glucose (P < 0.02),
with no difference between the two polyols. With the
glycemic index of glucose as 100, the indexes of xylitol
and lactitol were 7 and -1, respectively. A reactive
hypoglycemia was observed 3 h after glucose ingestion, but
not after the ingestion of sugar alcohols. There were no
significant changes in the carbohydrate or lipid oxidation
as determined by indirect calorimetry after the ingestion
of sugar alcohols. After glucose ingestion, the rise in
carbohydrate oxidation was nearly significant (P = 0.07).
In conclusion, lactitol and xylitol cause smaller changes
than does glucose in plasma glucose and insulin
concentrations and thermogenic response. A small hormonal
response and the lack of a thermogenic effect may be
beneficial when these sugar alcohols are used in food
products. The small glucose and insulin responses also
suggest that lactitol and xylitol are suitable components
of the diet for diabetic patients.
Alterations in
circulating fatty acids and the compartmentation of
selected metabolites in women with breast
cancer.
Quevedo-Coli S; Crespi C; Benito E; Palou A; Roca P
Departament de Biologia Fonamental i Ciencies de la Salut,
Universitat de les Illes Balears, Palma de Mallorca,
Spain.
Biochem Mol Biol Int (Australia) Jan 1997, 41 (1)
p1-10
The presence of the tumor in women with breast cancer
provokes a profile of biochemical change characterized by
hypoglycemia, hyperuremia and high levels of free fatty
acids and ketone bodies in plasma. The total circulating
levels of amino acids and lactate are slightly higher in
patients with breast cancer. Moreover, alterations in the
circulating levels of free and total fatty acids are
associated with enhanced levels of total free fatty acids
and significantly lower levels of esterified arachidonic
acid. This profile may indicate a state of moderate
catabolic activation in breast cancer patients and may also
be associated with a slight mobilization of proteins and
fatty acids by some of the peripheral tissues in order to
cover the needs of the host and the tumor. However, the
alteration in the distribution of different fatty acids
(saturated, mono-unsaturated and poly-unsaturated) and the
different behaviour of the free and esterified fractions
may be the result of a greater release of only specific
fatty acids by tumor or other host tissues, rather than a
higher release of the whole spectrum of free fatty acids.
Thus, it is proposed that some of the alterations may be
directly related to localized tumor activity.
Glutathione protects
against hypoxic/hypoglycemic decreases in 2-deoxyglucose
uptake and presynaptic spikes in hippocampal
slices.
Shibata S; Tominaga K; Watanabe S Department of
Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu
University, Fukuoka, Japan.
Eur J Pharmacol (Netherlands) Jan 24 1995, 273 (1-2)
p191-5
The effects of glutathione, its analogue: YM737
(N-(N-gamma-L-glutamyl-L- cysteinyl) glycine l-isopropyl
ester sulfate monohydrate), a monoester of glutathione, and
N-acetyl-L-cysteine on hypoxia/hypoglycemia-induced
decreases in CA1 presynaptic fiber spikes and
2-deoxyglucose uptake were investigated using rat
hippocampal slices. The drugs were added to normal medium
for 30 min before the incubation under hypoxic/hypoglycemic
conditions (20 min), and, after a 3-h washout, presynaptic
potential or 2-deoxyglucose uptake in hippocampal slices
was measured. Treatment with glutathione, YM737 and
N-acetyl-L-cysteine produced an attenuation of the
hypoxia/hypoglycemia-induced decrease in presynaptic fiber
spikes and 2-deoxyglucose uptake. The order of potency for
neuroprotective action was YM737 > or =
N-acetyl-L-cysteine > glutathione. The present
results suggest a role for glutathione in improving
hypoxia/hypoglycemia-induced dysfunction of hippocampal
regions.
|