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

Goodner, Charles J.; Freinkel, Norbert

doi:10.1172/jci104252

Cited by 40 publications

(7 citation statements)

References 36 publications

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“…The altered adrenocortical response seen in this study may be due to derangement of intrahypophyseal glucose metabolism as a result of relative insulin lack. 22 It is unlikely that such cortisol response in this study is related to noradrenergic activity, because plasma cortisol levels in normal man are unaffected by norepinephrine infusion, achieving a blood level fourfold greater than in our diabetic patients. 23 However, decreased plasma volume as a consequence of insulin administration may possibly be a responsible stimulus for cortisol release.…”

Section: Discussionmentioning

confidence: 53%

Counterregulatory Hormonal Responses to Rapid Glucose Lowering in Diabetic Man

et al. 1979

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To define whether rapid rate of fall in blood glucose stimulates counterregulatory hormonal responses in diabetic man, blood glucose in eight hyperglycemic diabetic subjects was rapidly lowered by intravenous insulin administration. Despite precipitous declines in blood glucose, plasma epinephrine and growth hormone remained virtually unchanged. In contrast, norepinephrine and cortisol increased significantly (P less than 0.025) in the face of hyperglycemia or euglycemia, while glucagon was suppressed (P less than 0.025). A transient modest fall in mean arterial pressure and a rise in pulse rate were noted. No correlation was observed between glucose disappearance rate or decrement in glucose concentration and the hormonal responses. After sham insulin administration, no change was observed in plasma epinephrine, norepinephrine, and cortisol levels. These findings suggest that rate of fall in blood glucose per se is not a primary signal for counterregulatory hormonal response. Cortisol but not growth hormone release during falling blood glucose in diabetic subjects can occur despite elevated blood glucose levels. The etiology of norepinephrine and cortisol change is unclear.

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Section: Discussionmentioning

confidence: 53%

Counterregulatory Hormonal Responses to Rapid Glucose Lowering in Diabetic Man

et al. 1979

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“…Presumptive abnormalities of both pituitary and gonadal function have been described in vivo (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). However, the interpretation of these observations is limited by confounding influences of weight loss, protein catabolism, hyperglycemia, gonadal vasculopathy, and homeostatic responses of the pituitary-gonadal and adrenal axes in intact animals (15)(16)(17)(18)(19)(20)(21)(22). Moreover, precise cellular or biochemical alterations responsible for gonadal dysfunction in diabetes mellitus have not been delineated.…”

mentioning

confidence: 99%

Mechanisms subserving the trophic actions of insulin on ovarian cells. In vitro studies using swine granulosa cells

Veldhuis¹,

Kolp²,

Toaff³

et al. 1983

J. Clin. Invest.

108

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A B S T R A C T Direct actions of insulin on gonadal tissues have been difficult to demonstrate in vivo. We have developed an in vitro system in which swine ovarian cells remain highly responsive to trophic actions of insulin. Purified porcine insulin significantly augmented the biosynthesis and secretion of progesterone by cultured granulosa cells. These stimulatory actions of insulin were dose-and time-dependent and saturable. Under serum-restricted conditions, insulin also significantly amplified the capacity of estradiol and 8-bromo cyclic AMP to stimulate progesterone production. Inhibitors of protein and RNA synthesis (cycloheximide, actinomycin D, and alpha-amanatin) inhibited insulin action. The stimulation of progesterone production by insulin was attributable to increased biosynthesis of pregnenolone, rather than diminished catabolism of progesterone to its principal metabolite, 20a-hydroxypregn-4-en-3-one. Insulin also enhanced progesterone production in the presence of a soluble sterol substrate, 5-cholesten-3j3,25-diol, which readily gains access to the mitochondrial cholesterol side-chain cleavage system. Moreover, exposure of granulosa cells to insulin produced a three-to sevenfold increase in mitochondrial content of cytochrome P-450 measured by difference spectroscopy, with a corresponding increase in mitochondrial cholesterol side-chain cleavage activity.The capacity of insulin to facilitate progesterone biosynthesis by ovarian cells was mimicked by the insulinlike somatomedin, multiplication stimulating activity, but not by epidermal growth factor, fibroblast growth factor, or porcine relaxin. Insulin's augmentation of progesterone production reflected a selective action on progestin biosynthesis, since insulin significantly suppressed estrogen biosynthesis by granulosa cells.Thus, our investigations indicate that insulin acts on ovarian cells selectively to stimulate pregnenolone (but not estrogen) biosynthesis. The actions of insulin are exerted by processes that require protein and RNA synthesis, and by mechanisms that augment mitochondrial cytochrome P-450 content and facilitate the utilization of cholesterol in the side-chain cleavage 1046 J. Clin. Invest.

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“…DIABETES 15: 115-22, February, 1966. Previous studies provided evidence for including the anterior pituitary among the insulin sensitive tissues. 1 This evidence included in vitro responses to insulin in the metabolism of glucose by anterior pituitary and documentation of changes in the glucose metabolism of glands collected from diabetic animals. Unanswered was the relative importance of glucose in anterior pituitary metabolism as a source of energy for protein synthesis From the Robert H. Williams Laboratory for Clinical Investigation, the Department of Medicine, the King County Hospital and the University of Washington School of Medicine, Seattle, Washington.…”

Section: Discussionmentioning

confidence: 99%

Effects of Insulin upon Glucose Metabolism and Protein Synthesis by the Anterior Pituitary in Vitro

Goodner

1966

Diabetes

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The effects of insulin upon the metabolism of glucose by single rat anterior pituitary glands in vitro have been compared with the effects of raising the concentration of glucose in the suspending medium. The pattern of stimulation with insulin differed from that induced by increasing glucose. Insulin enhanced glucose oxidation, glycogenesis and lipogenesis out of proportion to the increase in glucose uptake. The anterior pituitary exhibited relative insensitivity to insulin in vitro compared to muscle and adipose tissue. Stimulation of glucose metabolism was detectable at 1,000 uU. insulin per milliliter medium, and maximum stimulation occurred between 0.1 and 1.0 U. per milliliter. Insulin sensitivity was not altered by fasting. The effect of insulin was attenuated upon substituting phosphate for bicarbonate as buffer in the incubation medium. The incorporation of glycine C-14 into tissue protein was stimulated by insulin and this effect was undiminished in the absence of glucose in the medium. The incorporation of C-14-alpha-amino-isobutyric acid from the medium into the anterior pituitary was greater than that reported for rat diaphragm and was not affected by insulin. The data indicate that insulin could potentially affect hormonogenesis in anterior pituitary through stimulation of protein synthesis. The cell types responsive to insulin and the physiologic consequences of insulin activity upon the anterior pituitary remain to be established.

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

Cited by 40 publications

References 36 publications

Counterregulatory Hormonal Responses to Rapid Glucose Lowering in Diabetic Man

Counterregulatory Hormonal Responses to Rapid Glucose Lowering in Diabetic Man

Mechanisms subserving the trophic actions of insulin on ovarian cells. In vitro studies using swine granulosa cells

Effects of Insulin upon Glucose Metabolism and Protein Synthesis by the Anterior Pituitary in Vitro

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