Amount Of Exogenous Glucose Research Articles

Effect of chronic growth hormone and hyperinsulinemic euglycemia on endogenous glucose production and utilization in periparturient dairy cows

Twenty-one periparturient Holstein cows were used to assess the effects of chronic intramuscular growth hormone (GH) and hyperinsulinemic euglycemia (HE) on glucose rate of appearance (Ra) into plasma. Cows were administered intramuscular GH (40 mg) or saline (CTL) daily for 96 h beginning either 25 d prepartum (GH, n=5; CTL, n=6) or 5 d postpartum (GH, n=6; CTL, n=4). Glucose Ra into plasma was determined using tracer methodologies on d 4 of treatment during basal condition and again during a period of HE. The period of HE was initiated immediately after the basal period and lasted for 4 h. It involved a 2 μg*kg−1 infusion of bovine insulin with maintenance of glycemia within 10% of the pre-insulin baseline by intrajugular infusion of exogenous glucose. The HE decreased endogenous glucose Ra to a greater extent postpartum than it did prepartum (P<0.001). Chronic GH increased endogenous glucose Ra (P=0.03); however there were no interactions of GH with physiological state (pre- vs. postpartum) or degree of suppression of endogenous Ra by HE. The amount of exogenous glucose needed to maintain euglycemia during HE was not affected by GH (P≥0.20). In conclusion, there were no interactions of chronic GH with insulin relative to glucose metabolism. However, insulin did have differential effects on glucose metabolism during the pre-and postpartum periods. Project funded by internal sources.

Effect of differing antecedent hypoglycemia on counterregulatory responses to exercise in type 1 diabetes

Hypoglycemia frequently occurs during or after exercise in intensively treated patients with type 1 diabetes mellitus (T1DM), but the underlying mechanisms are not clear. In both diabetic and nondiabetic subjects, moderate hypoglycemia blunts counterregulatory responses to subsequent exercise, but it is unknown whether milder levels of hypoglycemia can exert similar effects in a dose-dependent fashion. This study was designed to test the hypothesis that prior hypoglycemia of differing depths induces acute counterregulatory failure of proportionally greater magnitude during subsequent exercise in T1DM. Twenty-two T1DM patients (11 males/11 females, HbA1c 8.0 +/- 0.3%) were studied during 90 min of euglycemic cycling exercise after two 2-h periods of previous day euglycemia or hypoglycemia of 3.9, 3.3, or 2.8 mmol/l (HYPO-3.9, HYPO-3.3, HYPO-2.8, respectively). Patients' counterregulatory responses (circulating levels of neuroendocrine hormones, intermediary metabolites, substrate flux, tracer-determined glucose kinetics, and cardiovascular measurements) were assessed during exercise. Identical euglycemia and basal insulin levels were successfully maintained during all exercise studies, regardless of blood glucose levels during the previous day. After day 1 euglycemia, patients displayed normal counterregulatory responses to exercise. Conversely, when identical exercise was performed after day 1 hypoglycemia of increasing depth, a progressively greater blunting of glucagon, catecholamine, cortisol, endogenous glucose production, and lipolytic responses to exercise was observed. This was paralleled by a graduated increase in the amount of exogenous glucose needed to maintain euglycemia during exercise. Our results demonstrate that acute counterregulatory failure during prolonged, moderate-intensity exercise may be induced in a dose-dependent fashion by differing depths of antecedent hypoglycemia starting at only 3.9 mmol/l in patients with T1DM.

Characterizing Lung Metabolism with Carbon-13 Magnetic Resonance Spectroscopy in a Small-Animal Model: Evidence of Gluconeogenesis during Hypothermic Storage

Experimental evidence suggests storing lungs inflated with oxygen and with oxidizable substrate improves results of lung transplantation. Glucose is included in the low-potassium-dextran (LPD) solution Perfadex to achieve this goal. The authors hypothesized that other substrates might be more effective. Rat lungs were stored for 6 or 24 hr in LPD solution with the following carbon-13--labeled substrates: 5 mM glucose (Perfadex group), 32 mM pyruvate (pyruvate group), or both (combination group). Metabolism was assessed by magnetic resonance spectroscopy. Small amounts of exogenous glucose were oxidized in the Perfadex group. In contrast, exogenous pyruvate was the major substrate oxidized in the pyruvate and combination groups (P<0.01 vs. Perfadex). Carbon-13--labeled glucose and glycogen were detected in the pyruvate group, suggesting that gluconeogenesis and glycogen synthesis occur in glucose-deprived lungs. Lungs for transplantation metabolize substrates through both anabolic and catabolic pathways. These reactions may be important in designing improved solutions for lung preservation.

The effects of dehydroepiandrosterone sulfate on counterregulatory responses during repeated hypoglycemia in conscious normal rats.

We previously determined that both antecedent hypoglycemia and elevated cortisol levels blunt neuroendocrine and metabolic responses to subsequent hypoglycemia in conscious, unrestrained rats. The adrenal steroid dehydroepiandrosterone sulfate (DHEA-S) has been shown in several studies to oppose corticosteroid action. The purpose of this study was to determine if DHEA-S could preserve counterregulatory responses during repeated hypoglycemia. We studied 40 male Sprague-Dawley rats during a series of 2-day protocols. Day 1 consisted of two 2-h episodes of 1) hyperinsulinemic (30 pmol. kg(-1). min(-1)) euglycemia (6.2 +/- 0.2 mmol/l; n = 12; ANTE EUG), 2) hyperinsulinemic euglycemia (6.0 +/- 0.1 mmol/l; n = 8) plus simultaneous intravenous infusion of DHEA-S (30 mg/kg; ANTE EUG + DHEA-S), 3) hyperinsulinemic hypoglycemia (2.8 +/- 0.1 mmol/l; n = 12; ANTE HYPO), or 4) hyperinsulinemic hypoglycemia (2.8 +/- 0.1 mmol/l; n = 8) with simultaneous intravenous infusion of DHEA-S (30 mg/kg; ANTE HYPO + DHEA-S). Day 2 consisted of a single 2-h hyperinsulinemic hypoglycemic (2.8 +/- 0.1 mmol/l) clamp. During the final 30 min of day 2, hypoglycemia norepinephrine levels were significantly lower in the ANTE HYPO group versus the ANTE HYPO + DHEA-S group (2.0 +/- 0.2 vs. 3.3 +/- 0.6 nmol/l; P < 0.05). In addition, epinephrine (8 +/- 1 vs. 17 +/- 2, 14 +/- 3, and 15 +/- 3 nmol/l), glucagon (91 +/- 8 vs. 273 +/- 36, 231 +/- 42, and 297 +/- 48 ng/l), and corticosterone (1,255 +/- 193 vs. 1,915 +/- 212, 1,557 +/- 112, and 1,668 +/- 119 pmol/l) were significantly lower in the ANTE HYPO group versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (P < 0.05). Endogenous glucose production was also significantly less in the ANTE HYPO group versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (13 +/- 5 vs. 32 +/- 3, 38 +/- 7, and 29 +/- 8 micro mol/l. kg(-1). min(-1); P < 0.05). Consequently, the amount of exogenous glucose needed to maintain the glycemic level during the clamp studies was significantly higher in the ANTE HYPO versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (57 +/- 8 vs. 22 +/- 5, 18 +/- 6, and 18 +/- 3 micro mol/l. kg(-1). min(-1); P < 0.05). In summary, day-1 antecedent hypoglycemia blunted neuroendocrine and metabolic responses to next-day hypoglycemia. However, simultaneous DHEA-S infusion during antecedent hypoglycemia preserved neuroendocrine and metabolic counterregulatory responses during subsequent hypoglycemia in conscious rats.

Effect of Antecedent Hypoglycemia on Counterregulatory Responses to Subsequent Euglycemic Exercise in Type 1 Diabetes

Exercise-related hypoglycemia is common in intensively treated patients with type 1 diabetes. The underlying mechanisms are not clearly defined. In nondiabetic subjects, hypoglycemia blunts counterregulatory responses to subsequent exercise. It is unknown whether this also occurs in type 1 diabetes. Therefore, the goal of this study was to test the hypothesis that prior hypoglycemia could result in acute counterregulatory failure during subsequent exercise in type 1 diabetes. A total of 16 type 1 diabetic patients (8 men and 8 women, HbA(1c) 7.8 +/- 0.3%) were investigated during 90 min of euglycemic cycling exercise, following either two 2-h periods of previous-day hypoglycemia (2.9 mmol/l) or previous-day euglycemia. Patients' counterregulatory responses (circulating levels of counterregulatory hormones, intermediary metabolites, substrate flux via indirect calorimetry, tracer-determined glucose kinetics, and cardiovascular measurements) were comprehensively assessed during exercise. Identical euglycemia and basal insulin levels were successfully maintained during all exercise studies, regardless of blood glucose levels during the previous day. After resting euglycemia, patients displayed normal counterregulatory responses to exercise. Conversely, when identical exercise was repeated after hypoglycemia, the glucagon response to exercise was abolished, and the epinephrine, norepinephrine, cortisol, endogenous glucose production, and lipolytic responses were reduced by 40-80%. This resulted in a threefold increase in the amount of exogenous glucose needed to maintain euglycemia during exercise. Our results demonstrate that antecedent hypoglycemia, in type 1 diabetes, can produce acute counterregulatory failure during a subsequent episode of prolonged moderate-intensity exercise. The metabolic consequence of the blunted neuroendocrine and autonomic nervous system counterregulatory responses was an acute failure of endogenous glucose production to match the increased glucose requirements during exercise. These data indicate that counterregulatory failure may be a significant in vivo mechanism responsible for exercise-associated hypoglycemia in type 1 diabetes.

Insulin sensitivity and fetal growth in ewes maintained in a moderate body condition compared with a lean body condition in late pregnancy

The possibility that an increase in maternal fatness might further enhance pregnancy-induced insulin insensitivity was investigated in ewes pregnant with one fetus. After selection of fat and lean ewes, they were fed to maintain maternal energy balance throughout pregnancy. A difference in insulin sensitivity of ewes in either a medium condition [score 2·9, 0·32± 0·031 kg fat/kg fat-free empty body (FFBW), n = 7] or lean body condition (score 2·0, 0·16±0.028 kg fat/kg FFBW, n = 8) at Day 136 of pregnancy was inferred by comparing their insulin response to an injection of glucose (350 mg/kg liveweight). The ewes were slaughtered at Day 146 of pregnancy to allow fetal weight, fetal fatness, and maternal fatness to be related to the capacity of the ewe to release insulin. The fatter ewes released more insulin in response to the injection of glucose (2. 54 log area units under the insulin response curve v. 2·22 for the lean ewes, pooled s.e. = 0·092, P &lt; 0·05), yet cleared the glucose from their blood streams at the same rate as the leaner ewes. Because the fat ewes required more insulin to remove a similar amount of exogenous glucose at a similar rate to the lean ewes, we suggest that the fat ewes were less sensitive to insulin. Further, the fetuses of the fatter ewes, while not different in total weight, had higher levels of body fat than those of the leaner ewes (29·4 v. 23·8 g/kg FFBW, pooled s.e. r = 1·32, P &lt; 0·05). Fetal fatness was also positively correlated to the magnitude of insulin release by the ewe (r = 0·61, P &lt; 0·05). Since glucose is the major precursor of fetal fat, these data support our contention that a reduction in maternal insulin sensitivity, brought on by an increase in maternal fatness, could partition more glucose to the fetus. If fat reserves aid lamb survival, lambs from fat ewes rather than lean ewes may have a better chance of survival, particularly in cold conditions.

A study of carbohydrate metabolism in the eggs (oncospheres) of the tapeworm,Hymenolepis diminuta, with special reference to glucose

When incubated in vitro for 24 h, intact eggs, chemically shelled eggs (obtained by treating intact eggs with NaOCl), activated larvae (eggs in which the outer shell and inner envelope were removed), and oncospheres (activated larvae treated with papain to remove the embryophore) absorb and metabolize radioactive glucose. Intact eggs, which are covered by the impermeable shell, absorb only small amounts of exogenous radioactive glucose, while chemically shelled eggs, activated larvae, and oncospheres absorb much larger amounts. Only very small amounts of the exogenous glucose are incorporated into the ethanol-precipitable carbohydrate fraction (which would include glycogen) by any of the preparations of eggs/larvae. However, the glucose is incorporated into higher molecular weight end-products that are liberated into the incubation medium. There is a temporal shift in the ability of activated larvae and oncospheres to metabolize exogenous glucose. Activated larvae and oncospheres absorb but do not metabolize glucose during the first 8 h post-activation. Between 8 and 16 h post-activation, however, virtually all of the absorbed glucose is metabolized into higher molecular weight end-products that are liberated into the incubation media. This temporal shift suggests that activation of oncospheres and cysticercoid morphogenesis are accompanied by distinct changes in carbohydrate metabolism.

Comparison of two methods for computing exogenous substrate oxidation using 13C-labeling

With 13C stable isotope as tracer, the purposes of this study were to measure the oxidation rates of exogenous glucose by using two computation procedures that take into account changes in isotopic composition of CO2 arising from oxidation of endogenous substrates (Rendo) and compare these results with studies using 14C-glucose. Two different low levels of 13C-enrichment were used in the first procedure, while a very high level of enrichment was used in the second one. Each of the eight subjects completed four exercises (68 +/- 5% VO2max; 90 min) on cycle ergometer, at 7-d intervals. After 30 min of exercise, the subjects ingested in a single bolus of 30 g of 13C-glucose, dissolved in 300 ml of water, enriched at three different levels (trials A and B = -10.9 and +2.5; trial C = +291.9/1000 delta 13C-PDB-1), or water only. The metabolic and endocrine state at rest and its response to exercise with or without glucose ingestion were similar in the four trials, with the exception of FFA and glycerol, which were blunted by the ingestion of glucose. As expected, Rendo significantly increased from rest (-22.7 +/- 0.7/1000 delta 13C-PDB-1) to the beginning of exercise without glucose ingestion (-21.2 +/- 0.5/1000 delta 13C-PDB-1). The amounts of exogenous glucose oxidized over the last hour of exercise and computed from trials A and B and from trial C were 14.9 +/- 4.4 and 13.0 +/- 4.2 g, representing 7.4 and 6.3% of the total energy requirement, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)