The A-and B-cells of the pancreatic islets as sources of the antagonistic hormones glucagon and insulin. The shift of the ab-relation in diabetes mellitus

Ferner, Helmut

doi:10.1007/bf02895538

Cited by 25 publications

(9 citation statements)

References 11 publications

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“…glucopenia and fell during glucose administration, fully consistent with its glycogenolytic and gluconeogenic actions (5-7). Glucagon was localized immunocytochemically to α cells of the pancreas (39), confirming the histochemical findings of Ferner (37). Nevertheless, the importance of its role continued to be debated, despite metabolic, physiologic, and anatomical clues suggesting a bihormonal homeostatic relationship between insulin and glucagon (12,40,41).…”

Section: Figuresupporting

confidence: 56%

“…In vivo evidence of its physiologic activity was provided by Foa's elegant pancreatic-femoral cross-circulation studies in dogs, which demonstrated that the pancreas was indeed the source of the hyperglycemic factor (36). Histochemical evidence reinforced the conclusion that glucagon came from pancreatic α cells (37).…”

Section: Endocrine and Paracrine Credentialsmentioning

confidence: 53%

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Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

2012

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The hormone glucagon has long been dismissed as a minor contributor to metabolic disease. Here we propose that glucagon excess, rather than insulin deficiency, is the sine qua non of diabetes. We base this on the following evidence: (a) glucagon increases hepatic glucose and ketone production, catabolic features present in insulin deficiency; (b) hyperglucagonemia is present in every form of poorly controlled diabetes; (c) the glucagon suppressors leptin and somatostatin suppress all catabolic manifestations of diabetes during total insulin deficiency; (d) total β cell destruction in glucagon receptor-null mice does not cause diabetes; and (e) perfusion of normal pancreas with anti-insulin serum causes marked hyperglucagonemia. From this and other evidence, we conclude that glucose-responsive β cells normally regulate juxtaposed α cells and that without intraislet insulin, unregulated α cells hypersecrete glucagon, which directly causes the symptoms of diabetes. This indicates that glucagon suppression or inactivation may provide therapeutic advantages over insulin monotherapy.Conflict of interest: Alan D.

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Section: Figuresupporting

confidence: 56%

Section: Endocrine and Paracrine Credentialsmentioning

confidence: 53%

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

2012

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“…Both of these effects, but particularly the effect of arginine, appear to be remarkably consistent in all subjects tested; a rise of at least 100 /qtg/ml has been observed during the infusion of 11.7 mg/kg per min of arginine in every one of 75 nondiabetic and dia-betic individuals studied thus far. The only exceptions have been patients with chronic pancreatitis reported elsewhere (6) (23). However, the present study provides the first direct evidence of increased glucagon levels in patients with diabetes mellitus.…”

Section: Relationship Of Therapy To Arginine-induced Glucagon Incremementioning

confidence: 46%

Studies of pancreatic alpha cell function in normal and diabetic subjects

Unger¹,

Aguilar-Parada²,

Müller³

et al. 1970

J. Clin. Invest.

799

360

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“…The fact that glucagon raises the blood glucose concentration has led a number of authors to suggest that it may be diabetogenic (6)(7)(8). Transient hyperglycemia, however, is not diabetes.…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

The Effect of Glucagon on Carbohydrate Metabolism in Normal Human Beings 1

Bondy¹,

Cardillo²

1956

J. Clin. Invest.

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Since the isolation of glucagon (hyperglycemicglycogenolytic factor, HGF) from the pancreas (1, 2), and the demonstration that it is released in appreciable amounts into the blood stream (3)(4)(5), there has been much speculation about the possibility that diabetes mellitus may result from an imbalance between secretion of insulin and glucagon (6)(7)(8). This speculation has been given additional weight by the demonstration that anterior pituitary growth hormone, a well established diabetogenic agent, causes release of a glucagonlike substance from the pancreas of experimental animals (5). The present investigation was undertaken to discover whether glucagon could produce an elevated blood glucose concentration with inhibition of glucose utilization, since this combination is usually observed in diabetic patients (9)(10)(11) Alpha amino nitrogen content of plasma and whole blood was determined on venous samples according to the method of Frame, Russell, and Wilhelmi (16,17).The concentration of blood ketone bodies was determined on arterial samples by a modification (18) of the method of Greenberg and Lester (19).In acute experiments, three control pairs of arteriovenous samples were drawn and then 1.0 ml. (0.95 mg.) of glucagon3 was immediately injected through the venous Cournand needle. Samples were taken 1, 2, 3, 5, 7, 10, and 15 minutes after the injection. A control experiment was run in two cases, by repeating the entire procedure, substituting a slow intravenous drip of 5 per cent glucose in water for glucagon. The rate of administration of glucose was adjusted to produce an arterial glucose curve approximating that produced by glucagon. The control experiments followed the glucagon experiments by at least one week.The effect of HGF on the peripheral circulation was studied by following skin temperatures and finger plethysmographs in two volunteers for fifteen minutes after the injection of glucagon. The subjects rested in a constant temperature room at 82 degrees F. for twentyfour minutes before the inj ections. Skin temperatures were measured in seven locations by thermocouples; relative blood flow was estimated by finger plethysmography, using the technique of Burch (20). No blood chemical determinations were made in these subjects.In a second group of subjects, 0.04 mg. per Kg. of glucagon was administered in 240 to 300 ml. of 0.9 per cent saline intravenously at a constant rate over the course of two hours. Control arterial and venous samples were drawn five minutes before and at the start of the glucagon infusion, and 15, 30, 60, and 120 minutes thereafter, while the glucagon was being administered. In 3 The glucagon preparation employed in these experiments, kindly supplied by Dr 494

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The A-and B-cells of the pancreatic islets as sources of the antagonistic hormones glucagon and insulin. The shift of the ab-relation in diabetes mellitus

Cited by 25 publications

References 11 publications

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

Studies of pancreatic alpha cell function in normal and diabetic subjects

The Effect of Glucagon on Carbohydrate Metabolism in Normal Human Beings 1

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