Disturbance of Carbohydrate Metabolism in Normal Dogs Injected with the Hypophyseal Growth Hormone.

Evans, Herbert M.; Meyer, Karl; Simpson, Miriam E.; Reichert, Frederick Leet

doi:10.3181/00379727-29-6114

Cited by 66 publications

(9 citation statements)

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“…Houssay, 1 -2 Evans, 3 and Young 4 first demonstrated the diabetogenic effect of growth hormone (GH). A comprehensive review on the subject was published by Sirek and Sirek.…”

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confidence: 99%

Insulin Secretion in Rats with Elevated Levels of Circulating Growth Hormone Due to MtT-W15 Tumor

1968

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Circulating levels of growth hormone (GH) in "WistarFurth rats bearing the MtT-\V15 tumor are twenty to thirty times higher than normal. The effect of constantly elevated levels of GH on the pancreatic islets was studied. Tumor-bearing rats (TR) and normal controls (C) were pair-fed for seven weeks. In TR, fasting serum levels of GH and insulin were 599 ± 157 ng./ml. and.142 ± 43 /iU./ml., respectively, and only 18.2 ± 1.9 ng./ml. and 26.9 ± 7.9 /iU./ml., respectively, in the controls. The islets of TR were enlarged with an islet/acinar ratio of 3.38 per cent (C: 0.82 per cent). The extracted pancreatic insulin was 9.84 ± 0.9 mU./mg. (C: 5.36 ± 0.4 mU./mg.). Incubated slices or isolated islets of TR pancreas released greater amounts of insulin when submitted to glucose stimulation. Incorporation of labeled leucine into insulin was increased also in TR. An exaggerated insulin response to a glucose load was found in vivo (peak value at 30 min., TR: 183 dt 42.5 fiU./ml; C: 71 ± 17.9 /*U/ml.). None of the TR became diabetic, however, and two to six weeks after removal of the tumors serum GH levels had returned to normal (17.2 /ig./ml.) as had insulin levels both fasting (19.0 /iU/ml.) and following a glucose load (56.4 fiU./mg.). Insulin output by incubated pancreas decreased 50 per cent (26 fiU./mg.). The islet/acinar ratio returned to normal but the insulin content remained high. These re g "ltft mAi.. cate that in animals exposed to hjyh levels of endogenous GH there is an increased responsiveness of the islets to glu-UTABETES J/:bol-OV, lNovember, !Vo8.

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“…Houssay, 1 -2 Evans, 3 and Young 4 first demonstrated the diabetogenic effect of growth hormone (GH). A comprehensive review on the subject was published by Sirek and Sirek.…”

mentioning

confidence: 99%

Insulin Secretion in Rats with Elevated Levels of Circulating Growth Hormone Due to MtT-W15 Tumor

1968

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“…Evans et al [2] subsequently found diabetogenic activity in an anterior pituitary extract and attributed it to growth hormone. Four years later Lyall and Innes [3] reported a case of dia betes mellitus in man where the development of hypopi tuitarism led to an amelioration of the metabolic state.…”

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confidence: 99%

Growth Hormone and Diabetes mellitus

1993

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The diabetogenic action of pituitary extracts containing growth hormone has been recognised for more than 60 years and the importance of growth hormone in the development and progression of diabetic retinopathy for more than 30 years. Hypophysectomy was the first effective treatment for retinopathy but was discontinued because of the risk of severe hypoglycaemia that it produced and the development of an alternative, less dangerous therapy -photocoagulation. The precise role and significance of growth hormone in diabetes care, however, remains to this day a mystery. The fact that modern, highly purified biosynthetic preparations of growth hormone still retain full diabetogenic potency and the fact that diabetes develops in up to 25% of patients with acromegaly indicate growth hormone’s potential for involvement in the aetiology of diabetes mellitus, although most will agree that this is not likely to be an important factor in the large majority of ‘idiopathic’ cases. There is strong evidence to indicate a substantial hypersecretion of growth hormone in ‘idiopathic’ diabetes mellitus (particularly insulin-dependent cases and those with retinopathy), which appears to be more related to residual pancreatic insulin secretion than to metabolic control. Since the advent of biosynthetic growth hormone in sufficient quantity to perform trials in adults, we are more aware of growth hormone’s considerable potency in the regulation of body composition, growth factor production and intermediary metabolism. In this article, we review the literature and, from this and our own work, propose a new hypothesis which links the hypersecretion of growth hormone to reduced hepatic secretion of insulin-like growth-factor I (IGF-I) as a direct result of reduced portal insulin levels in diabetes mellitus. The hypersecretion of growth hormone exposes peripheral organs such as the retina and kidney to conditions favouring the expression of growth-hormone-dependent growth factors such as IGF-I which may contribute to the development of diabetic microvascular disease by autocrine and/or paracrine effects. If this hypothesis proves to be true, it offers new opportunities for the prevention of diabetic microvascular complications through suppression of growth hormone secretion which in turn will increase insulin sensitivity and facilitate good glycaemic control.

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“…Significant abnormalities in blood sugar were not observed at any time intervals in the partial or sham pancreatectomized groups. Respective values for blood sugar in these groups were 84 mg per 100 ml [2] and 58 ± 4 mg per 100 ml [5] 5 hours following surgery, and 107 ± 5 mg per 100 ml [4] and 102 + 6 mg per 100 ml [13] at sacrifice.…”

Section: (Carbohydrate Metabolism Of Surviving Anteriormentioning

confidence: 90%

Studies of Anterior Pituitary Tissue in Vitro: Effects of Insulin and Experimental Diabetes Mellitus Upon Carbohydrate Metabolism*

Goodner¹,

Freinkel²

1961

J. Clin. Invest.

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Since the classical experiments of Houssay and Biasotti (1), Evans, Meyer, Simpson and Reichert (2), Young (3), and Long and Lukens (4), the diabetogenic potential of pituitary hormones has been amply documented (5). However, the metabolism of glucose by the pituitary has received but little examination (6-9), and the authors have been unable to find any published studies of the hormonal determinants of hypophyseal carbohydrate economy. Because of the potential contribution of these factors to the endocrine function of the pituitary, experiments were initiated to define the role of insulin. The studies have demonstrated that the assimilation and disposition of glucose by surviving preparations of anterior pituitary from normal rats and beef may be enhanced by insulin in vitro. Moreover, it has been shown that glucose metabolism is significantly reduced in anterior pituitaries excised from rats rendered insulin-deficient by total pancreatectomy or alloxanization, and that these hypophyseal derangements can be prevented by replacement therapy with insulin in vivo. METHODS

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Disturbance of Carbohydrate Metabolism in Normal Dogs Injected with the Hypophyseal Growth Hormone.

Cited by 66 publications

References 0 publications

Insulin Secretion in Rats with Elevated Levels of Circulating Growth Hormone Due to MtT-W15 Tumor

Insulin Secretion in Rats with Elevated Levels of Circulating Growth Hormone Due to MtT-W15 Tumor

Growth Hormone and Diabetes mellitus

Studies of Anterior Pituitary Tissue in Vitro: Effects of Insulin and Experimental Diabetes Mellitus Upon Carbohydrate Metabolism*

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