Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.
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PMID:Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans. 389 86

The aim of this study was to compare the effects of fructose (F) and glucose (G) intake before exercise on oxidation of the ingested substrate, glycogen utilization, work output, and metabolic changes. Ten trained subjects ingested F or G (1 g/kg), both of which were naturally enriched in 13C. After 1 h of rest, they exercised on an ergometer at 61% of their maximal oxygen uptake (VO2 max) for 45 min, which was immediately followed by 15 min at their maximal voluntary output. During the resting hour, blood insulin and glucose were lower (p less than 0.05) and respiratory quotient and blood lactate higher (p less than 0.01) after F. During exercise, the differences disappeared, apart from a transient but moderate (4.3 mmol/l) hypoglycemia after G compared to F. No difference between F and G was observed for uric acid, glycerol, FFA, and glucagon. Glycogen decrements in the vastus lateralis muscle were 67 +/- 9 (F) and 97 +/- 15 (G) mmol/kg, values not significantly different from each other (P greater than 0.05). The maximal voluntary work produced during the last 15 min did not differ between treatments. During the 2 h after sugar ingestion, 30 +/- 3 g of F and 26 +/- 3 g of G were oxidized to 13CO2. These findings indicate that fructose ingested before exercise was utilized at least as well as glucose, allowed a more stable glycemia, and did not modify performance.
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PMID:Oxidation and metabolic effects of fructose or glucose ingested before exercise. 390 79

The hormonal responses to low-level exercise in pregnancy have been studied in 13 insulin-requiring diabetic patients and 42 control subjects. We found no significant changes in plasma glucose, epinephrine, glucagon, or FFA with this level of exercise in the study group and control subjects; but plasma norepinephrine showed a significant increase with exercise. This type of exercise appears to be safe and could serve as a model for exercise prescription for attaining improved glucose tolerance in pregnant diabetic women.
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PMID:Hormonal responses to exercise in diabetic and nondiabetic pregnant patients. 399 70

We have used multiple isotope infusions to study the integrated response of glucose, fat, and protein metabolism to combined alpha + beta-adrenergic blockade in conscious, unstressed, fasting (15 h) dogs. The response to the blocking agents was evaluated both with and without control of the glucoregulatory hormones. The hormones were controlled at the basal level by infusions of somatostatin and metyrapone to block their secretion, and by the infusion of insulin, glucagon, growth hormone, and cortisol at physiological rates. We found that adrenergic blockade markedly inhibited lipolysis, as reflected by falls in glycerol and plasma FFA appearance. The decrease in fat mobilization after blockade resulted in a proportionate shift from fat as an energy substrate toward carbohydrate. Glucose production and oxidation were both enhanced after blockade. The source of the increased glucose production was presumably hepatic glycogen because urea production was presumably hepatic glycogen because urea production was unaffected and glycerol uptake was decreased. These results are consistent with the interpretation that basal adrenergic activity plays an important role in the mobilization of fat in fasting dogs. A secondary consequence of that action is apparently a diminution of glucose production and oxidation, although the mechanism responsible for the latter response is not clear.
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PMID:Investigation of kinetics of integrated metabolic response to adrenergic blockade in conscious dogs. 611 65

In an attempt to define the relationship between plasma insulin and triglyceride concentrations, we have studied the effect of suppression of the postprandial insulin response upon the secretion and plasma concentration of very low density lipoprotein (VLDL)-triglycerides. Eight nondiabetic subjects with a wide range of fasting plasma triglyceride levels (100-358 mg/dl) were studied during three dietary periods: base line, high carbohydrate (80% calories), and high carbohydrate (80% calories) with a daily intravenous infusion of somatostatin (SRIF) (1.3 micrograms/min) between 800 and 2,100 h. The significant increase in postprandial insulin response observed during high carbohydrate vs. base line was completely abolished during high carbohydrate-SRIF. However, plasma triglyceride levels rose in all subjects during each high carbohydrate period (with/without SRIF) vs. base line and the mean values reached during each period were the same (476 +/- 165 vs. 482 +/- 152 mg/dl, respectively). The secretion of VLDL-triglyceride into plasma was higher in four subjects, the same in two subjects, and lower in one subject during high carbohydrate-SRIF vs. high carbohydrate alone. The mean production rate of VLDL-triglyceride (mg/kg per h) was 25.6 +/- 4.9 during the high carbohydrate and 40.9 +/- 28.1 during the high carbohydrate-SRIF periods. These values were not significantly different. Postprandial glucose levels were slightly increased during high carbohydrate-SRIF, but overnight glucose concentrations were not affected. Plasma FFA levels were not different during the two high carbohydrate periods. Plasma glucagon levels did not appear to affect the results either. This study indicates that postprandial hyperinsulinemia during a high carbohydrate diet is not necessary for induction of hypertriglyceridemia.
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PMID:Effect of somatostatin-induced suppression of postprandial insulin response upon the hypertriglyceridemia associated with a high carbohydrate diet. 612 60

Since the initial proposal of the glucose fatty acid cycle, considerable controversy has arisen concerning its physiologic significance in vivo. In the present study, we examined the effect of acute, physiologic elevations of FFA concentrations on glucose production and uptake in normal subjects under three controlled experimental conditions. In group A, plasma insulin levels were raised and maintained at approximately 100 microU/ml above base line by an insulin infusion, while holding plasma glucose at the fasting level by a variable glucose infusion. In group B, plasma glucose concentration was raised by 125 mg/100 ml and plasma insulin was clamped at approximately 50 microU/ml by a combined infusion of somatostatin and insulin. In group C, plasma glucose was raised by 200 mg/100 ml above the fasting level, while insulin secretion was inhibited with somatostatin and peripheral glucagon levels were replaced with a glucagon infusion (1 ng/min X kg). Each protocol was repeated in the same subject in combination with a lipid-heparin infusion designed to raise plasma FFA levels by 1.5-2.0 mumol/ml. With euglycemic hyperinsulinemia (study A), lipid infusion caused a significant inhibition of total glucose uptake (6.3 +/- 1.3 vs. 7.4 +/- 0.6 mg/min X kg, P less than 0.02). Endogenous glucose production (estimated by the [3-3H]glucose technique) was completely suppressed both with and without lipid infusion. With hyperglycemic hyperinsulinemia (study B), lipid infusion also induced a marked impairment in glucose utilization (6.2 +/- 1.1 vs. 9.8 +/- 1.9 mg/min X kg, P less than 0.05); endogenous glucose production was again completely inhibited despite the increase in FFA concentrations. Under both conditions (A and B), the percentage inhibition of glucose uptake by FFA was positively correlated with the total rate of glucose uptake (r = 0.69, P less than 0.01). In contrast, when hyperglycemia was associated with relative insulinopenia and hyperglucagonemia (study C), thus simulating a diabetic state, lipid infusion had no effect on glucose uptake (2.9 +/- 0.2 vs. 2.6 +/- 0.2 mg/min X kg) but markedly stimulated endogenous glucose production (1.4 +/- 0.5 vs. 0.5 +/- 0.4 mg/min X kg, P less than 0.005). Under the same conditions as study C, a glycerol infusion producing plasma glycerol levels similar to those achieved with lipid-heparin, enhanced endogenous glucose production (1.5 +/- 0.5 vs. 0.7 +/- 0.6 mg/min X kg, P less than 0.05). We conclude that, in the well-insulinized state raised FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. When insulin is deficient, on the other hand, elevated rates of lipolysis may contribute to hyperglycemia not by competition for fuel utilization, but through an enhancement of endogenous glucose output.
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PMID:Effect of fatty acids on glucose production and utilization in man. 613 67

The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double-blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p = 0.037 and p = 0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p = 0.0036 and p = 0.0003), respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
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PMID:Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients. 614 67

The hypothesis was made of an increased oxidation of fatty acids (FFA) and a decrease of their esterification rate contributing to the islet secretory defect during starvation. 2-Bromostearate (BrS), a FFA-oxidation inhibitor, was therefore tested on the islet secretion of insulin, glucagon and somatostatin stimulated by glucose or palmitate under fasted or fed conditions. Starvation for 48 h blocked both the glucose-induced stimulation and inhibition of insulin and somatostatin and the glucagon secretion. BrS completely restored the insulin response and stimulated both somatostatin and glucagon-basal release, the latter inhibition by glucose being partially recovered. Palmitate transient stimulation of insulin and somatostatin and inhibition of glucagon release was turned into a sustained increase in all three cases by addition of BrS. The potentiation by BrS of palmitate secretory effects in "fed" islets and of hormone release in "fasted" islets, apparently suggest that inhibition of FFA-oxidation may play a role in the regulation of islet secretion.
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PMID:Starvation-induced secretory changes of insulin, somatostatin, and glucagon and their modification by 2-bromostearate. 614 16

Somatostatin (ST)-induced glucagon suppression results in hypoglycemia during rest and exercise. To further delineate the role of glucagon and interactions between glucagon and the catecholamines during exercise, we compensated for the counterregulatory responses to hypoglycemia with glucose replacement. Five dogs were run (100 m/min, 12 degrees) during exercise alone, exercise plus ST infusion (0.5 micrograms/kg-min), or exercise plus. ST plus glucose replacement (3.5 mg/kg-min) to maintain euglycemia. During exercise alone there was a maximum increase in immunoreactive glucagon (IRG), epinephrine (E), norepinephrine (NE), FFA, and lactate (L) of 306 +/- 147 pg/ml, 360 +/- 80 pg/ml, 443 +/- 140 pg/ml, 541 +/- 173 mu eq/liter, and 6.3 +/- 0.7 mg/dl, respectively. Immunoreactive insulin (IRI) decreased by 10.2 +/- 4 micro/ml and cortisol (C) increased only slightly (2.1 +/- 0.3 micrograms/dl). The rates of glucose production (Ra) and glucose uptake (Rd) rose markedly by 6.6 +/- 2.2 mg/kg-min and 6.2 +/- 1.5 mg/kg-min. In contrast, when ST was given during exercise, IRG fell transiently by 130 +/- 20 pg/ml, Ra rose by only 3.6 +/- 0.5 mg/kg-min, and plasma glucose decreased by 29 +/- 6 mg/dl. The decrease in IRI was no different than with exercise alone (10.2 +/- 2.0 microU/ml). As plasma glucose fell, C, FFA, and L rose excessively to peaks of 5.4 +/- 1.3 micrograms/dl, 1,166 +/- 182 mu eq/liter and 15.5 +/- 7.0 mg/dl. The peak increment in E (765 +/- 287 pg/ml) coincided with the nadir in plasma glucose and was four times greater than during normoglycemic exercise. Hypoglycemia did not affect the rise in NE. The increase in Rd was attenuated and reached a peak of only 3.7 +/- 0.8 mg/kg-min. During glucose replacement, IRG decreased by 109 +/- 30 pg/ml and the IRI response did not differ from the response to normal exercise. Ra rose minimally by 1.5 +/- 0.3 mg/kg-min. The changes in E, C, Rd, and L were restored to normal, whereas the FFA response remained excessive. In all protocols increments in Ra were directly correlated to the IRG/IRI molar ratio while no correlation could be demonstrated between epinephrine or norepinephrine and Ra. In conclusion, (a) glucagon controlled approximately 70% of the increase of Ra during exercise. This became evident when counterregulatory responses to hypoglycemia (E and C) were obviated by glucose replacement; (b) increments in Ra were strongly correlated to the IRG/IRI molar ratio but not the plasma catecholamine concentration; (c) the main role of E in hypoglycemia was to limit glucose uptake by the muscle; (d) with glucagon suppression, glucose production was deficient but a further decline of glucose was prevented through the peripheral effects of E, (e) the hypoglycemic stimulus for E secretion was facilitated by exercise; and (f) we hypothesize that an important role of glucagons during exercise could be to spare muscle glycogen by stimulating glucose production by the liver.
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PMID:Interactions between glucagon and other counterregulatory hormones during normoglycemic and hypoglycemic exercise in dogs. 614 56

In normal humans, infusion of epinephrine for 4 h increased plasma epinephrine to 411 +/- 38 pg/ml but had no significant effect on palsma insulin or glucagon levels. Epinephrine produced a prompt 45% rise in glucose output (P less than 0.01) and a 120% rise in FFA (P less than 0.001), both of which declined to basal levels by 60-90 min. Glucose clearance decreased by 25% (P less than 0.005) and remained suppressed for 4 h. The binding of [125I]hydroxybenzylpindolol to lymphocytes was unchanged after epinephrine infusion. We conclude that in normal humans 1) physiological increments in epinephrine have a persistent effect in decreasing glucose clearance but only transiently increase hepatic glucose output and FFA levels and 2) this refractoriness of liver and adipose tissue to epinephrine occurs without a concomitant decrease in beta-adrenergic binding to lymphocytes.
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PMID:Effects of physiological infusion of epinephrine in normal humans: relationship between the metabolic response and beta-adrenergic binding. 610 51


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