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Biomedical subjects

R K Kalkhoff

Publications and source records attributed to R K Kalkhoff.

68 records · Page 4Linked to original sources
PubMed1971

Relative effects of pregnancy, estradiol, and progesterone on plasma insulin and pancreatic islet insulin secretion.

Influences of estrogen and progesterone on the development of hyperinsulinemia and augmented pancreatic islet insulin secretion during pregnancy were assessed in this study. Groups of female rats were injected subcutaneously for 21 days with varying daily dosages of estradiol benzoate or progesterone in oil. On day 21, pancreatic islets were isolated by a collagenase method. Total insulin secretion was measured after 90-min incubations of 10 islets in buffered medium containing glucose. Higher physiologic dosages of estradiol or progesterone, singly or in combination, significantly increased islet secretion above values of untreated control rats and were comparable to augmented islet responses of term, 3-wk pregnant rats. Diameter and protein content of islets obtained from steroid-treated and pregnant rats exceeded control measurements in these instances. However, 2-hr preincubations of control islets with 1 or 10 mug/ml of either steroid did not influence subsequent glucose-stimulated insulin output. In related studies, plasma insulin responses during 30 min intravenous glucose tolerance tests were significantly above control responses in term-pregnant rats and animals receiving comparable dosages of steroids for 3 wk. Unlike pregnancy or progesterone treatment, estradiol administration alone or with progesterone significantly lowered postchallenge plasma glucose concentrations. These results indicate that estradiol and progesterone contribute to enhanced islet insulin secretion and plasma insulin responses to glucose administration during pregnancy. This change is not acutely produced but can be related to hypertrophy of islets following chronic hormonal administration. Although the data do not distinguish between direct and indirect beta-cytotrophic effects of these sex steroids, metabolic actions of estradiol and progesterone may differ, since estrogen treatment lowers plasma glucose curves following the induction of hyperinsulinemia.

Animals↗
PubMed1971

Plasma insulin disturbances in primary hyperparathyroidism.

Plasma insulin dynamics were evaluated in 10 patients with primary hyperparathyroidism before and after parathyroidectomy and correction of hypercalcemia. Before surgery fasting plasma insulin concentrations and insulin responses to administered glucose, tolbutamide, and glucagon were significantly greater than postoperative values. Hyperinsulinemia was not associated with altered glucose curves during glucose or glucagon tolerance tests, but a relatively greater insulin response to tolbutamide resulted in an increased hypoglycemic effect following its administration. The glucose-lowering action of intravenous insulin was slightly impaired before treatment. Intramuscular injections of parathormone to six normal men for 8 days induced mild hypercalcemia and hypophosphatemia and reproduced augmented plasma insulin responses to oral glucose and intravenous tolbutamide. 4-hr intravenous infusions of calcium to another group of six normal men raised serum calcium concentrations above 11 mg/100 ml. This did not alter glucose or insulin curves during oral glucose tolerance but markedly accentuated insulin responses to tolbutamide and potentiated its hypoglycemic effect. When highly purified parathormone was incubated with isolated pancreatic islets of male rats, glucose-stimulated insulin secretion was unaffected. These findings suggest that chronic hypercalcemia of hyperparathyroidism sustains a form of endogenous insulin resistance that necessitates augmented insulin secretion to maintain plasma glucose homeostasis. This state is insufficient to oppose tolbutamide-induced hypoglycemia because of an additional direct, selective enhancement of hypercalcemia on pancreatic beta cell responsiveness to the sulfonylurea. The possible direct role of parathormone in these events has not been established.

Adenoma↗
PubMedDate not supplied

The influence of hormonal changes of pregnancy on maternal metabolism.

Mammalian pregnancy is characterized by progressive hyperinsulinaemia, raised plasma lipids and increased vulnerability to ketosis after food deprivation. The present investigations were performed to assess the role of two placental steroids, oestradiol and progesterone, in the development of these changes, since plasma titres of these hormones progressively increase during human gestation. In both human subjects and adult female rats it was demonstrated that these two steroids, separately or in combination, augment plasma insulin concentration in vivo, cause hypertrophy of pancreatic islets and promote exaggerated secretion of insulin, but not glucagon, by pancreatic islets in vitro. Hypertriglyceridaemia induced by oestrogen alone or combined with progesterone was associated with increased splanchnic production of triglyceride as well as altered tissue lipoprotein lipase (EC 3.1.1.34) and circulating apoproteins that influence activity of this enzyme. The combined regimen also increased hepatic glycogen storage and suppressed gluconeogenesis in vivo in the rat while accelerating the onset of ketosis during starvation in human subjects and in the animal model. Oestradiol and progesterone appear to effect metabolic changes in nonpregnant animals and human subjects that simulate maternal adaptations to advancing gestation, including altered endocrine pancreatic function, triglyceride metabolism and metabolic fuel storage and mobilization.

Animals↗
PubMedDate not supplied

The saccharin controversy.

Saccharin and its salts are the most extensively consumed artificial sweeteners in the United States today. The current controversy about the risks of their use to human health has surfaced from research findings that report an increased incidence of cancer, primarily of the urinary bladder, in certain animal species and man chronically exposed to these agents. The April 1977 proposal by the Food and Drug Administration to restrict use of saccharin was based on these investigations. The intense public response against any ban has led to Congressional deliberations over the fate of saccharin during the present moratorium and information-gathering period. Since diabetic patients are among the principal users of this compound, it appears timely to review the evidence for and against its carcinogenic potential.

Adolescent↗
PubMedDate not supplied

Relative sensitivity of postpartum gestational diabetic women to oral contraceptive agents and other metabolic stress.

Women who develop diabetes mellitus during pregnancy very often revert to normal carbohydrate metabolism after parturition. During this quiescent period, however, increased sensitivity to adverse metabolic stress is evident. Recurrence of impaired carbohydrate tolerance with greater frequency than in normal populations is observed following the administration of oral contraceptive agents, glucocorticoids, and certain placental hormones such as human chorionic somatomammotropin. Factors responsible for this vulnerability to adverse stress are unknown but, in part, may reside in subclinical defects in beta-cell function. Ultimately, the great majority of these individuals develop permanent disease, suggesting that diabetes initially manifested only during pregnancy is not transient but progresses to more severe forms later in life.

Blood Glucose↗