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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoglucagonemia (induced by somatostatin) and hyperglucagonemia (induced by infusion of physiologic amounts of glucagon) have only evanescent effects on blood glucose regulation. Despite on-going glucagon suppression by somatostatin, fasting hyperglycemia develops within 4-6 hr of insulin suppression, indicating that (1) basal glucagon secretion is not essential for the development of the diabetic state; and (2) insulin-deficiency (rather than altered glucagon secretion) is the dominant long-term factor determining glucose homeostasis in the diabetic. With respect to hyperglucagonemia, only a transient increase in splanchnic glucose output is observed in normal and diabetic subjects in response to physiologic increments in this hormone. The exaggerated hyperglycemic effect of glucagon observed in diabetics1 is thus a consequence of the failure to metabolize the glucose traniently released into the systemic circulation in response to the glucagon rather than a result of persistent stimulation of hepatic glucose production. These observations thus further underscore the essentiality of insulin deficiency in the diabetogenic action of glucagon.
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PMID:Evanescent effects of hypo- and hyperglucagonemia on blood glucose homeostasis. 97 38

The case history of a patient with serious hypoglycemia (with 0.6-3 mmol/l blood glucose) persisting for eight years and treated as epilepsy during the time of observation is reported. As the cause of hypoglycemia hyperinsulinemia, hypoglucagonemia, and moderate adrenal insufficiency was suggested. The pattern of secretion of insulin as well as of C-peptide indicated, that hyperinsulinemia was induced by hypersecretion of immunoreactive insulin. As the cause of hypersecretion of insulin insulinoma might have been ruled out. Hypoglucagonemia was shown by the low concentration of plasma glucagon. Adrenal insufficiency seemed to be due to ACTH deficiency. Replacement therapy with dexamethasone or administration of ACTH led to elevation of the blood glucose to normal, and the plasma cortisol also reached normal levels. On the basis of other data as well as of our own investigations we suggest a central origin of the illness. The patient has been free from his complaints with normal blood glucose and plasma cortisol concentrations for two years.
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PMID:Persistent hypoglycemia due to hyperinsulinemia, hypoglucagonemia and mild adrenal insufficiency. 282 82

The effect of a two hour period of hypo- and hyperglucagonemia on a subsequent insulin-induced hypoglycemia was studied in nine healthy volunteers. Hypoglucagonemia was provoked by somatostatin (50 micrograms/h) and hyperglucagonemia by glucagon infusion (3.25 ng/kg/min) together with somatostatin, while saline alone was given as control. Hypoglycemia was induced by insulin infusion (2.4 U/h) for two hours. The hyperglycemic effect of glucagon was transient and similar nadir glucose levels were obtained in the three experiments. Preinfusion with glucagon impaired glucose recovery in spite of preserved secretion of epinephrine during restitution of blood glucose in this experiment. It is concluded, that a period of elevated glucagon levels deteriorates the restitution of blood glucose following hypoglycemia. Hyperglucagonemia, commonly apparent in poorly controlled diabetics, may therefore be of importance in explaining the impaired recovery of blood glucose seen in such patients after hypoglycemia.
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PMID:Pre-exposure to glucagon impairs glucose recovery after insulin-induced hypoglycemia in man. 288 57

This study examined the effects of hypoglucagonaemia and hyperglucagonaemia on the incorporation of 14C from [2-(14)C]propionate into plasma glucose of sheep in vivo. The sheep were adult ewes fed a maintenance diet of lucerne pellets delivered in equal aliquots hourly. The irreversible loss of glucose was determined by the continuous infusion of [6-(3)H]glucose. During the control period (the hour immediately preceding infusion of hormones) 63 +/- 2% of the propionate was converted to glucose, accounting for 30 +/- 2% of glucose production. Glucagon deficiency, induced by infusion of somatostatin (100 micrograms/h), did not affect gluconeogenesis and the irreversible loss of glucose significantly. However, glucagon infusion at 11.5 +/- 0.6 micrograms/h significantly increased the irreversible loss of glucose, with the greatest increase occurring in the first 15 min of infusion. The 14C specific radioactivity of glucose and the fraction of glucose derived from propionate decreased significantly during glucagon infusion. The data are consistent with glucagon have a marked glycogenolytic effect initially, but little or no selective effect in promoting the utilization of propionate for glucose synthesis in vivo in sheep.
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PMID:Effects of somatostatin and glucagon on the utilization of [2-(14)C]propionate in glucose production in vivo in sheep. 610 57

The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is not solely attributable to dissipation of insulin and, therefore, must also involve factors that actively raise the plasma glucose concentration--glucose counterregulatory factors. We have shown that the secretion of two of these, glucagon and epinephrine, is specific for glucose ingestion and temporally related to the glucose counterregulatory process. To determine the physiologic roles of glucagon and epinephrine in postprandial glucose counterregulation, we produced pharmacologic interventions that resulted in endogenous glucagon deficiency with and without exogenous glucagon replacement, adrenergic blockade, and adrenergic blockade coupled with glucagon deficiency starting 225 min after the ingestion of 75 g of glucose in normal subjects. Also, we assessed the effect of endogenous epinephrine deficiency alone and in combination with glucagon deficiency late after glucose ingestion in bilaterally adrenalectomized subjects. Glucagon deficiency resulted in nadir plasma glucose concentrations that were approximately 30% lower (P less than 0.01) than control values, but did not cause hypoglycemia late after glucose ingestion. This effect was prevented by glucagon replacement. Neither adrenergic blockade nor epinephrine deficiency alone impaired the glucose counterregulatory process. However, combined glucagon and epinephrine deficiencies resulted in a progressive fall in mean plasma glucose to a hypoglycemic level late after glucose ingestion; the final glucose concentration was 40% lower (P less than 0.02) than the control (epinephrine deficient) value in these patients, and was nearly 50% lower (P less than 0.001) than the control value and approximately 30% lower (P less than 0.05) than the glucagon-deficient value in normal subjects. We conclude (a) the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion. (b) Epinephrine does not normally play a critical role in this process, but enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon secretion is deficient.
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PMID:Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion. 613 7

Glucagon may regulate FFA metabolism in vivo. To test this hypothesis, six healthy male volunteers were infused with somatostatin, to inhibit endogenous hormone secretion, and insulin, glucagon, and GH to replace endogenous secretion of these hormones. In the hypoglucagonemia experiments, the glucagon infusion was omitted, and in the hyperglucagonemic experiments glucagon was infused at 1.3 ng/kg.min, to produce physiological hyperglucagonemia. In two sets of control experiments, glucagon was infused at 0.65 ng/kg.min, in order to maintain peripheral euglucagonemia, and the plasma glucose concentrations were clamped at the levels observed in either the hypo- or hyperglucagonemic experiments. Rates of FFA and glycerol (an index of lipolysis) appearance (Ra) were estimated with the isotope dilution method using [1-14C]palmitate and [2H5] glycerol. Plasma glucagon concentrations decreased during the hypoglucagonemic experiments (85 +/- 12 vs. 123 +/- 22 ng/L, P < 0.05) and increased during the hyperglucagonemic experiments (186 +/- 20 vs. 125 +/- 15 ng/L, P < 0.05), whereas other hormone concentrations remained the same. Hypoglucagonemia resulted in equivalent suppression of FFA Ra (3.7 +/- 0.2 vs. 5.9 vs. 0.3 mumol/kg.min, P < 0.01) and glycerol Ra (1.2 +/- 0.2 vs. 2.2 +/- 0.5 mumol/kg.min, P < 0.05). Similarly, hyperglucagonemia resulted in equivalent stimulation of FFA Ra (5.2 +/- 0.4 vs. 3.7 +/- 0.3 mumol/kg.min, P < 0.05) and glycerol Ra (1.5 +/- 0.3 vs. 1.1 +/- 0.1 mumol/kg.min, P < 0.05). These results indicate that glucagon has a physiological role in the regulation of FFA metabolism in vivo.
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PMID:Regulation of free fatty acid metabolism by glucagon. 832 59

Pancreatic resection results in hormonal abnormalities that are dependent on the extent and location (proximal versus distal) of the resected portion of the gland. The form of glucose intolerance which results from pancreatic resection is termed pancreatogenic diabetes. It is associated with features distinct from both type I (insulin-dependent) and type II (insulin-independent, or adult-onset) diabetes. Hepatic insulin resistance with persistent endogenous glucose production and enhanced peripheral insulin sensitivity result in a brittle form of diabetes which can be difficult to manage. In addition to insulin deficiency, the endocrine abnormalities that accompany pancreatic resection can include glucagon deficiency or pancreatic polypeptide (PP) deficiency if the resection is distal or proximal, respectively. Glucagon deficiency can contribute to iatrogenic hypoglycemia, and PP deficiency can contribute to persistent hyperglycemia due to impaired hepatic insulin action. Pancreatic resections that spare the duodenum, such as distal pancreatectomy, duodenum-preserving pancreatic head resection (Beger procedure), or extended lateral pancreaticojejunostomy with excavation of the pancreatic head (Frey procedure), are associated with a lower incidence of new or worsened diabetes than the standard or pylorus-preserving pancreaticoduodenectomy (Whipple procedure) or total pancreatectomy. Operative considerations for the treatment of pancreatic disease should include strategies to minimize the hormonal impairment of pancreatic resection.
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PMID:Pancreatic resection: effects on glucose metabolism. 1134 98