Hyperglucagonemia in diabetic ketoacidosis

Müller, W.; Faloona, Gerald R.; Unger, Roger H

doi:10.1016/0002-9343(73)90083-1

Cited by 213 publications

(90 citation statements)

References 22 publications

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“…The infusion caused an increase to four fold the normal glucagon concentration, i.e. the levels observed in poorly controlled juvenile diabetes [10]. GFR increased promptly in all subjects and remained elevated throughout the infusion period.…”

Section: Resultsmentioning

confidence: 80%

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The effect of short-term glucagon infusion on kidney function in normal man

et al. 1977

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Summary. Kidney function was studied in six normal males before and during a 2 h glucagon (10ng/kg/min) infusion. The following variables were determined during each 20 min clearance period; glomerular filtration rate (GFR), renal plasma-flow (RPF), filtration fraction (FF), urinary albumin and/32-microglobulin-excretion rates. Glucagon infusion resulted in a fourfold increase in plasma glucagon concentration. The infusion induced a significant increase in GFR (+9%), FF (+ 9%) and urinary fl2-microglobulin excretion rate (+ 32%), (p < 0.01). RPF and urinary albumin excretion rates were not significantly changed. We suggest that glucagon may contribute to the reversible kidney function alterations typically found in poorly regulated juvenile diabetes, a state with relative or absolute hyperglucagonaemia.

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Section: Resultsmentioning

confidence: 80%

“…Hyperglucagonaemia is present in poorly controlled diabetes [10]. Enhanced GFR has been demonstrated in animals and man during glucagon infusion in pharmacological doses [1, 3,7].…”

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confidence: 99%

The effect of short-term glucagon infusion on kidney function in normal man

et al. 1977

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“…Glucagon secreted by pancreatic a-cells regulates glucose homeostasis by promoting hepatic glucose production. Plasma glucagon levels are increased under both fasting and postprandial states in diabetes (2,3). This hyperglucagonemia increases hepatic glucose production, thereby contributing importantly to diabetic hyperglycemia (4,5).…”

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confidence: 99%

Blockade of Na+ Channels in Pancreatic α-Cells Has Antidiabetic Effects

et al. 2014

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Pancreatic a-cells express voltage-gated Na + channels (NaChs), which support the generation of electrical activity leading to an increase in intracellular calcium, and cause exocytosis of glucagon. Ranolazine, a NaCh blocker, is approved for treatment of angina. In addition to its antianginal effects, ranolazine has been shown to reduce HbA 1c levels in patients with type 2 diabetes mellitus and coronary artery disease; however, the mechanism behind its antidiabetic effect has been unclear. We tested the hypothesis that ranolazine exerts its antidiabetic effects by inhibiting glucagon release via blockade of NaChs in the pancreatic a-cells. Our data show that ranolazine, via blockade of NaChs in pancreatic a-cells, inhibits their electrical activity and reduces glucagon release. We found that glucagon release in human pancreatic islets is mediated by the Na v 1.3 isoform. In animal models of diabetes, ranolazine and a more selective NaCh blocker (GS-458967) lowered postprandial and basal glucagon levels, which were associated with a reduction in hyperglycemia, confirming that glucose-lowering effects of ranolazine are due to the blockade of NaChs. This mechanism of action is unique in that no other approved antidiabetic drugs act via this mechanism, and raises the prospect that selective Na v 1.3 blockers may constitute a novel approach for the treatment of diabetes.

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“…The observations in severe derangements of diabetic control include elevated plasma levels of glucagon [3], cortisol [4], growth hormone [5,6], and catecholamines [7,8]. The hierachy of their pathogenetic significance, however, remains to be established.…”

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confidence: 99%

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

et al. 1981

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Summary. To evaluate the relative role of "diabetogenic" hormones as insulin antagonists in severe derangements of diabetic control, glucagon, cortisol, growth hormone and adrenaline were administered by continuous intravenous infusion, separately and in combination, to ketosis-prone insulin-dependent diabetics (n = 11). The amount of insulin required for the assimilation of a 50 g glucose load during the various hormone infusions was determined by means of an automated glucose-controlled insulin infusion system and used as an index of insulin effectiveness. Raising plasma hormone concentrations acutely into the range seen in severe diabetic states (glucagon 517+_70pg/ml; cortisol 32-+3gg/dl; growth hormone 14+3ng/ml) did not alter significantly blood glucose profile and insulin requirement (control ll.3_l.lU; glucagon 11.6-+2.0U; cortisol 11.1_+0.4 U; growth hormone 12.9___1.4 U), except for adrenaline (plasma level 550_+ 192 pg/ml), which caused a marked rise in blood glucose levels and a threefold increase in insulin demand (31.1_+ 3.7 U). Combined infusion of all hormones did not potentiate significantly the latter effect (38.3___4.7 U). The effectiveness of metabolic control by insulin was assessed by a marked decrease in plasma nonesterified free fatty acids and ketone bodies upon its administration after glucose ingestion in all groups studied. It is concluded that from the hormones investigated within this study adrenaline exerts the strongest diabetogenic action during its short term administration followed by that of growth hormone. Whereas it may well be that over-insulinization of the patients by the glucose controlled insulin infusion system has overcome and disguised the smaller diabetogenic effects of cortisol and glucagon.Key words: Diabetes mellitus, counter-regulatory hormones, glucagon, cortisol, growth hormone, adrenaline, insulin, non-esterified fatty acids, ketone bodies.Excess secretion of insulin-counteracting hormones is claimed to be important in the metabolic changes and insulin resistance in diabetic ketoacidosis [1,2]. The observations in severe derangements of diabetic control include elevated plasma levels of glucagon [3], cortisol [4], growth hormone [5,6], and catecholamines [7,8]. The hierachy of their pathogenetic significance, however, remains to be established. Hyperglycaemia, decreased glucose tolerance and insulin resistance have been demonstrated under certain circumstances after exogenous administration of these hormones [9][10][11][12]. Furthermore, the above mentioned counter-regulatory hormones are known to exert lipolytic and ketogenic activity when elevated to high physiological concentrations in insulin deficient diabetic man [12][13][14][15][16]. The delay in the development of ketoacidosis in insulin-withdrawn diabetics by either somatostatin-induced suppression of growth hormone and glucagon [17] or following pituitary ablation [1] serves as further support for implicating these hormones as pathogenic factors of deranged metabolic control. In addition, circulator...

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Hyperglucagonemia in diabetic ketoacidosis

Cited by 213 publications

References 22 publications

The effect of short-term glucagon infusion on kidney function in normal man

The effect of short-term glucagon infusion on kidney function in normal man

Blockade of Na+ Channels in Pancreatic α-Cells Has Antidiabetic Effects

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

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