The Role of Glucagon Deficiency in the Houssay Phenomenon of Dogs

Nakabayashi, Hajime; Dobbs, R. E.; Unger, Roger H

doi:10.1172/jci109053

Cited by 17 publications

(6 citation statements)

References 21 publications

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“…February1980 The present findings showed that the elevated plasma glucose level and gut GI due to pancreatectomy fell down significantly in almost parallel with each other after hypophysectomy. These results were in agreement with the report of Nakabayashi et al(1978).…”

Section: Discussionsupporting

confidence: 94%

The effect of hypophysectomy and hypophysis-trans-plantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs.

Yoshida

Kondo

1980

Endocrinol Japon

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SynopsisThe role of hypophysis in the regulation mechanism of the secretion of gut glucagon immunoreactivity (gut GI) that was measured using C-terminal specific glucagon antiserum after pancreatectomy, and gut glucagon-like immunoreactivity (gut GLI) that was obtained by subtracting GI from total glucagon-like immunoreactivity (total GLI) which was measured using non-specific glucagon antiserum, was investigated in depancreatized dogs.Plasma glucose, gut GI and gut GLI levels were found to increase in totally depancreatized dogs. The former two showed a significant decrease after hypophysectomy, and were reversed by the hypophysis-transplantation, while gut GLI was not affected either by hypophysectomy or hypophysis-transplantation. Intramuscular injections of human growth hormone (HGH) or adrenocorticotropic hormone-Z (ACTH-Z) to depancreatized-hypophysectomized dogs had no effect on plasma glucose level or gut GI.It is concluded that hypophysis may promote the secretion of gut GI after pancreatectomy, but not of gut GLI. Gut GI seems to regulate plasma glucose level after pancreatectomy.However, the precise regulation mechanism of gut GI by the hypophysial hormone after pancreatectomy is not clarified yet.

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Section: Discussionsupporting

confidence: 94%

The effect of hypophysectomy and hypophysis-trans-plantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs.

Yoshida

Kondo

1980

Endocrinol Japon

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“…However, in the 1970s, several groups reported measurable glucagon levels in insulin-deprived, totally pancreatectomized humans and animals (62-65). The stomach was found to be an important source of the nonpancreatic hyperglucagonemia, and classical α cells were found in the gastric fundus and duodenum of animals and humans (66,67). Gastric α cells were shown to oversecrete glucagon during insulin deficiency and to be more sensitive than pancreatic α cells to small amounts of insulin.…”

Section: Glucagon Sine Qua Non Of Hyperglycemia In All Forms Of Insumentioning

confidence: 99%

“…These insights invalidated the only argument against an essential diabetogenic role for glucagon (67). Glucagonocentrism had become plausible.…”

Section: Glucagon Sine Qua Non Of Hyperglycemia In All Forms Of Insumentioning

confidence: 99%

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

2012

Self Cite

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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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“…11 Hypophysectomized dogs have decreased postabsorptive insulin concentrations 1213 and suppressed basal and arginine-stimulated plasma glucagon levels. 14 Furthermore, hypophysectomy reduces hepatic glucose production and peripheral glucose uptake. 15 Since treatment of such hypophysectomized dogs with growth hormone or cortisol restores normal glucose turnover rates, 1617 it is not inconceivable that the lack of these hormones together with reduced plasma glucagon levels could be responsible for the decreased glucose production seen after hypophysectomy in normal dogs.…”

mentioning

confidence: 99%

“…1214 In these dogs totally devoid of insulin, hypophysectomy decreased basal and argininestimulated secretion of extrapancreatic glucagon 14 and prevented ketoacidosis, but rarely normalized the hyperglycemia. Amelioration of the diabetic state was probably due to at least three factors: lack of pituitary hormones and reduction of adrenocortical hormones and glucagon in plasma.…”

mentioning

confidence: 99%

Glucoregulatory Mechanisms Following Hypophysectomy in Diabetic Dogs with Residual Insulin Secretion

Kemmer¹,

Sirek²,

Sirek³

et al. 1983

Diabetes

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It is known that in pancreatectomized dogs completely deprived of insulin, hypophysectomy normalizes plasma glucagon and prevents ketoacidosis, but rarely normalizes glucose levels. The present study concerns diabetic dogs with only partial insulin deficiency in whom we studied the effects of hypophysectomy on glucoregulatory mechanisms. Eleven dogs were alloxanized and hypophysectomized 2-3 wk later. Withholding exogenous insulin from alloxan-diabetic dogs resulted in hypoinsuiinemia (6 ± 1 |xU/ml), hyperglucagonemia (341 ± 44 pg/ml), elevated plasma FFA levels (1442 ± 1 2 5 jxeq/ml), hyperglycemia (333 ± 27 mg/dl), increased hepatic glucose production (Ra, 4.2 ± 0.3 mg/kg/min) and decreased clearance of glucose (CR, 1.8 ± 0.1 ml/kg/min). After hypophysectomy, glucagon and FFA fell to normal in 7 of 11 hypophysectomized alloxan-diabetic dogs (106 ± 7), while 4 remained hyperglycemic (337 ± 28 mg/dl). Normoglycemia was the result of a reduced Ra to subnormal in the presence of unaltered glucose clearance. However, normoglycemia could not be equated with normal metabolism: glucose turnover was well below normal, and peripheral glucose uptake was impaired. The sensitivity of the liver to glucagon was investigated by infusing somatostatin alone (ST, 0.24 jig/kg/min) and with replacement (1 mg/kg/min) or with excess of glucagon (3.6 ng/kg/min). Even in hypophysectomized dogs, glucagon suppression resulted in a sustained decrease in Ra and plasma glucose. Glucagon replacement restored glucose kinetics and excess of glucagon led to hyperglycemia (300 ± 20 mg/dl). This was due to a prompt rise in Ra which, however, plateaued at levels lower than in diabetic dogs, suggesting that normalization of glucagon following hypophysectomy is an important but not the sole factor responsible for the marked reduction in Ra. The persistence of hyperglycemia in four diabetic dogs was attributed to a diminished effect of the hypophysectomy: in spite of hyperglycemia, Ra was not lower than in normoglycemic dogs, it was insensitive to glucagon suppression, and glucose clearance was more impaired than in normoglycemic dogs. It is hypothesized, therefore, that these dogs had a smaller residual insulin reserve than normoglycemic hypophysectomized dogs. Thus a critical amount of insulin may be indispensible for the maintenance of normoglycemia.In conclusion, in alloxan-diabetic dogs, hypophysectomy can fully normalize postabsorptive glycemia, due to suppression of glucose production. Normoglycemia is, however, associated with an abnormally low glucose turnover. Hyperglucagonemia is important but not the sole factor responsible for diabetic overproduction of glucose. Hypophysectomy does not abolish the hepatic sensitivity to glucagon in insulin-deficient dogs. Persistence of hyperglycemia in some dogs after hypophysectomy is associated with less effective suppression of glucose production and with a very low glucose clearance. DIABETES 32:26-34, January 1983.

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The Role of Glucagon Deficiency in the Houssay Phenomenon of Dogs

Cited by 17 publications

References 21 publications

The effect of hypophysectomy and hypophysis-trans-plantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs.

The effect of hypophysectomy and hypophysis-trans-plantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs.

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

Glucoregulatory Mechanisms Following Hypophysectomy in Diabetic Dogs with Residual Insulin Secretion

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