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)

Methyl palmoxirate, an effective hypoglycemic agent administered p.o., has been shown to decrease hepatic glucose production secondary to inhibition of mitochondrial fatty acid oxidation. Because the ability to increase hepatic glucose production is an important counter-regulatory defense against hypoglycemia, we compared the ability of streptozotocin/alloxan-induced diabetic dogs treated p.o. with vehicle or methyl palmoxirate (2.5 mg/kg/day X 7 days) to recover from insulin-induced hypoglycemia. Hepatic glucose production and glucose utilization were determined by isotope dilution before and after acute reduction of plasma glucose by i.v. insulin injection (0.10 or 0.13 U/kg). Diabetic dogs treated with methyl palmoxirate for 6 days had lower overnight fasting plasma glucose levels than vehicle-treated animals (158 +/- 7 vs. 171 +/- 11, respectively, P less than .05). Plasma glucose at 4 hr after the last dose of drug decreased to 115 +/- 5 mg/dl, whereas glucose in the vehicle-treated dogs was unchanged (172 +/- 8 mg/dl). Recovery from insulin-induced hypoglycemia (nadirs of 58 +/- 5 and 42 +/- 4 mg/dl in the vehicle- and methyl palmoxirate-treated groups, respectively) was not significantly different between the two groups of dogs. Restoration of plasma glucose was primarily due to increased hepatic glucose production in both treatment groups, as glucose utilization did not fall significantly below baseline levels. Plasma glucagon levels increased in both vehicle- and methyl palmoxirate-treated dogs in response to hypoglycemia, indicating that release of an important counter-regulatory hormone was not compromised by drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the fatty acid oxidation inhibitor methyl palmoxirate (methyl 2-tetradecylglycidate) on recovery from insulin-induced hypoglycemia in diabetic dogs. 267 19

Regional difference in secretion of glucagon and insulin from the rat pancreatic islets and their contents in pancreatic tissue and islets were studied. The glucagon content in the normal rat pancreas was the highest at the splenic part followed in order by the gastric, choledochal and duodenal parts. The effect of alloxan on the glucagon content was stronger in the dorsal lobe (combined gastric and splenic parts) than in the ventral lobe (combined duodenal and choledochal parts), and more increase of glucagon was found. The size of pancreatic islets was similar between the dorsal and the ventral lobe. The glucagon content in the islets was significantly higher in the dorsal lobe than in the ventral lobe, but the insulin content in the islets was similar in both lobes. The release of insulin from cultured pancreatic islets from the dorsal lobe was similar to that from the ventral lobe, but the release of glucagon was significantly high from the cultured islets of the former in the presence of glucose or arginine compared with that from the latter. Also in isolated pancreatic islets the release of glucagon was significantly more marked in the islets from the dorsal lobe by arginine administration. These findings show that the islets from the dorsal lobe secrete and contain more glucagon than those from the ventral lobe in contrast to there being a similar amount of release of insulin between them.
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PMID:Contents and secretion of glucagon and insulin in rat pancreatic islets from the viewpoint of their localization in pancreas. 269 12

The effects of beta-selective blockade with metoprolol on the glucagon blood plasma level during insulin-induced hypoglycemia were studied in 20 control dogs, and 20 alloxan diabetic dogs. The results indicate that the sensitivity to exogenous insulin is increased in alloxan diabetes glucose counterregulatory mechanisms are impaired. After insulin administration glucagon concentration increased much more and quicker in the control group than in diabetic dogs. Beta-blockade with metoprolol increased glucagon secretion in both groups.
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PMID:[Effects of beta-selective blockade on levels of glucagon in blood plasma during insulin-induced hypoglycemia]. 270 37

Insulin-deficient diabetes in man as well as in experimental diabetes is associated with islet cell insensitivity to glucose. The present study was designed to determine whether this abnormality could be counteracted either by increasing the intraislet insulin level or by normalizing the diabetic state by a glucose-controlled insulin infusion system (GCIIS: Biostator, Life Science Instruments, Elkhart, Indiana). Using the isolated, perfused pancreas of dogs with moderate, untreated alloxan diabetes of 4 days duration, we found that 5 mM arginine (N = 4) and 5 mM calcium (N = 4) stimulated D- and A-cell secretion, whereas an increment in glucose from 1.3 to 11 mM (N = 4) had no effect on islet hormone secretion. In the pancreas from untreated alloxan-diabetic dogs, acute infusion of large amounts of insulin (25 mU/ml) in vitro simultaneously with an elevation of perfusate glucose from 1.3 to 11 mM failed to restore the glucose from 1.3 to 11 mM failed to restore the glucose sensitivity. In contrast, treatment of alloxan-diabetic dogs (N = 3) by a GCIIS for 24 h revived some responsiveness of the glucagon, insulin, and somatostatin to glucose (1.3-11 mM) of the subsequently perfused pancreas. It is concluded that the insensitivity to glucose of islet cells in insulin-deficient diabetes is not ascribed to an intra-islet insulin deficiency per se but rather to an abnormal metabolic state secondary to insulin deficiency. The results also indicate that the glucose receptor dysfunction is not due to a direct lesion by the diabetogenic drug.
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PMID:Reversal of D- and A-cell insensitivity to glucose in alloxan-diabetic dogs by treatment with the artificial beta cell (Biostator). 285 68

Treatment with thiazide diuretics causes an impairment of the glucose metabolism. To study whether this is due to a direct effect on the endocrine pancreas, the effects of the thiazide hydroflumethiazide on the release of glucagon, insulin, and somatostatin from the isolated perfused pancreas of normal and alloxan diabetic dogs were examined. Hydroflumethiazide at concentrations ranging from 1 to 50 micrograms/mL stimulated the normal secretion of glucagon (P less than 0.001), insulin (P less than 0.001), and somatostatin (P less than 0.001) in a dose-dependent manner. The normal hormone responses evoked by 50 micrograms/mL of the thiazide were, however, modified by the prevailing glucose level: higher insulin (P less than 0.05) and somatostatin (P less than 0.05) and lower glucagon (P less than 0.05) were obtained at the high glucose concentration of 11 mmol/L rather than at the low glucose concentration of 1.3 mmol/L. In alloxan diabetes, insulin secretion was almost extinct and did not respond to hydroflumethiazide, whereas glucagon was dose-dependently stimulated (P less than 0.001). In addition, we looked at the effect of the loop diuretic, bumetanide. The infusion of bumetanide at doses ranging from 0.5 to 3 micrograms/mL did not alter the release of glucagon, insulin, and somatostatin in the presence of 5.5 mmol/L glucose. The results suggest that hydroflumethiazide possesses the ability to directly stimulate A cell secretion in the normal and alloxan diabetic pancreas. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during thiazide therapy remains, however, uncertain.
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PMID:Effects of a thiazide diuretic (hydroflumethiazide) and a loop diuretic (bumetanide) on the endocrine pancreas: studies in vitro. 286 65

To define the role of immunoreactive glucagon (IRG) during exercise in diabetes, 12 insulin-deprived alloxan-diabetic (A-D) dogs were run for 90 min (100 m/min, 12 degrees) with or without somatostatin (St 0.5 microgram . kg-1 . min-1). Compared with normal dogs, A-D dogs were characterized by similar hepatic glucose production (Ra), lower glucose metabolic clearance, and higher plasma glucose and free fatty acid levels during rest and exercise. In A-D dogs IRG was greater at rest and exhibited a threefold greater exercise increment than controls, whereas immunoreactive insulin (IRI) was reduced by 68% at rest but had similar values to controls during exercise. Basal norepinephrine, epinephrine, cortisol, and lactate levels were similar in normal and A-D dogs. However, exercise increments in norepinephrine, cortisol, and lactate were higher in A-D dogs. When St was infused during exercise in the A-D dogs, IRG was suppressed by 432 +/- 146 pg/ml below basal and far below the exercise response in A-D controls (delta = 645 +/- 153 pg/ml). IRI was reduced by 1.8 +/- 0.2 microU/ml with St. With IRG suppression the increase in Ra seen in exercising A-D controls (delta = 4.8 +/- 1.6 mg . kg-1 . min-1) was virtually abolished, and glycemia fell by 104 to 133 +/- 37 mg/dl. Owing to this decrease in glycemia, the increase in glucose disappearance was attenuated. Despite the large fall in glucose during IRG suppression, counterregulatory increases were not excessive compared with A-D controls. In fact, as glucose levels approached euglycemia, the increments in norepinephrine and cortisol were reduced to levels similar to those seen in normal exercising dogs. In conclusion, IRG suppression during exercise in A-D dogs almost completely obviated the increase in Ra, resulting in a large decrease in plasma glucose. Despite this large fall in glucose, there was no excess counterregulation, since glucose concentrations never reached the hypoglycemic range.
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PMID:Important role of glucagon during exercise in diabetic dogs. 286 45

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10-12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes. 286 46

We have previously shown that the antidiabetic property of fenugreek seeds (Trigonella foenum graecum L.) is associated with the defatted seed material which is rich in fibers, saponins, and proteins. In the present work this defatted preparation was divided into two subfractions: subfraction "a" which contains the testa and endosperm and is rich in fibers (79.6%); and subfraction "b" which contains the cotyledons and axes and is rich in saponins (7.2%) and proteins (52.8%). We investigated the effects of each subfraction on hyperglycemia and the levels of pancreatic hormones when chronically administered to alloxan-diabetic dogs. Each subfraction was studied separately and was given to the dogs per os (mixed with the two daily meals), in addition to the insulin treatment (which was kept the same throughout the experiment) for a period of 21 days. The addition of subfraction "a" to insulin treatment resulted in a clear decrease of hyperglycemia and glycosuria accompanied by a reduction of the high plasma glucagon and somatostatin levels in diabetic dogs. The treatment also decreased the hyperglycemic response to the oral glucose tolerance test. In contrast the chronic administration of subfraction "b" had no effect on hyperglycemia or on the levels of pancreatic hormones in diabetic dogs. Our results show that the antidiabetic properties of fenugreek seeds are contained in the testa and endosperm. Although this subfraction is rich in fibers (high viscosity; 115 cP), it is not possible to exclude the existence of one or more unknown active pharmacological compounds in this subfraction of the seed.
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PMID:Antidiabetic effects of subfractions from fenugreek seeds in diabetic dogs. 287 58

The glucagon-suppressing activity of insulin and somatostatin were compared at high and low glucose concentrations. In normal dogs made hyperglucagonemic by phloridzin pretreatment, insulin and somatostatin suppressed glucagon at rates of 47 +/- 8 and 35 +/- 8%/h (NS), respectively, despite profound hypoglycemia. In severely hyperglycemic alloxan-diabetic dogs, insulin and somatostatin suppressed glucagon at rates of 48 +/- 13 and 54 +/- 6%/h, respectively, not different from the nondiabetic dogs. After phloridzin pretreatment to eliminate hyperglycemia in the diabetic dogs, insulin and somatostatin suppressed 51 +/- 8 and 31 +/- 10%/h (NS), respectively. Glucose infused in the phloridzin-pretreated insulin-deprived group suppressed glucagon only partially; insulin was required to reduce it further. We conclude that insulin and somatostatin suppress glucagon at similar rates irrespective of ambient glucose levels, and that diabetic hyperglucagonemia represents the summation of stimulation by insulin lack minus suppression by the associated hyperglycemia.
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PMID:Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration. 287 38

In order to determine the role of glucagon in futile or substrate cycling in diabetes, we measured tracer determined glucose kinetics during a combined infusion of 2-3H-glucose (total glucose production) and 6-3H-glucose (glucose production) in six alloxan-diabetic dogs. The animals received either a 420 min infusion of (1) somatostatin alone (0.3 microgram X kg-1 X min-1), (2) somatostatin with insulin replacement (100 microU X kg-1 X min-1) or (3) glucagon (6 ng X kg-1 X min-1) together with somatostatin and transient insulin replacement. When somatostatin was given alone, plasma glucagon (p less than 0.004) and insulin (p less than 0.0001) were suppressed. Glucose production and disappearance and plasma glucose concentrations fell (p less than 0.0001), but the metabolic clearance of glucose did not change significantly. In the basal state, futile cycling comprised 29 +/- 4%, 33 +/- 4% and 33 +/- 3% of total glucose production in the three groups of studies, which is high compared to normal dogs. The absolute rate of futile cycling fell slightly but significantly from 10.0 +/- 1.7 to 8.3 +/- 1.7 mumol X kg X -1 min-1 (p less than 0.0008). When insulin replacement was given during somatostatin infusion to correct for the small somatostatin-induced insulin suppression, there were similar changes in plasma glucagon, glucose concentrations and glucose kinetics as seen during the infusion of somatostatin alone. Futile cycling decreased to a slightly greater extent from 12.8 +/- 2.8 to 9.5 +/- 1.7 mumol X kg-1 X min.-1 (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Importance of glucagon in the control of futile cycling as studied in alloxan-diabetic dogs. 288 59


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