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Biomedical subjects

M B Davidson

Publications and source records attributed to M B Davidson.

At least 109 records · Page 6Linked to original sources
PubMed1985

Pathogenesis of impaired glucose tolerance and type II diabetes mellitus--current status.

The insulin response to glucose taken orally is increased in patients with impaired glucose tolerance (IGT) but decreased in those with type II diabetes mellitus. The insulin response to meals, however, is normal in patients with type II diabetes, although the glucose concentrations are obviously elevated. The acute insulin response to intravenously administered glucose is absent in cases of both IGT and type II diabetes when the fasting plasma glucose level exceeds 115 mg per dl. On the other hand, the response to other intravenously given secretagogues is either normal or nearly so. The absent acute insulin response to intravenously administered glucose can be restored by alpha-adrenergic blockade, prostaglandin synthesis inhibition, dopaminergic blockade and euglycemia. Insulin antagonism characterizes patients with both IGT and type II diabetes. Those with IGT and mild diabetes mellitus (untreated fasting plasma glucose concentrations < 180 mg per dI) have a receptor defect probably due to down regulation. Diabetic patients with more severe type II diabetes show a postreceptor defect. The relation (if any) between receptor and postreceptor defects is unclear.

Administration, Oral↗
PubMed1984

Insulin resistance of late pregnancy does not include the liver.

Hyperinsulinemia was required to preserve normal intravenous glucose tolerance in late pregnancy in the rat (18 to 21 days' gestation). To evaluate the site and mechanism of this insulin resistance, insulin binding and action were measured in hepatocytes freshly isolated from control and gravid animals. As expected, glucose concentrations were lower, insulin levels were higher, and hepatocyte size increased in the pregnant animals. Insulin binding was similar in liver cells from the two groups. No difference was found in sensitivity or responsiveness of insulin-stimulated net 14C-glucose incorporation into glycogen in the hepatocytes from the control and gravid rats. These results suggest that the well-documented, but ill-defined, insulin antagonism of late pregnancy does not include the liver and is a postreceptor defect, most likely residing in muscle tissue.

Alanine↗
PubMed1983

Hepatic insulin effects independent of changes in Ca++ metabolism.

The possibility of Ca++ acting as second messenger for insulin in rat liver was investigated using the net stimulation of 14C-glucose incorporation into glycogen by isolated hepatocytes as an index of insulin action. An insulin effect could be partially sustained in the virtual absence of Ca++ and Mg++ and a maximal insulin effect could be observed in the presence of either Ca++ or Mg++, suggesting that extracellular Ca++ is not required for insulin action. Inhibiting the activity of calmodulin, an intracellular mediator of Ca++ action, with trifluoperazine had little effect on insulin action. The efflux of 45Ca from prelabeled hepatocytes was not altered by the presence of insulin arguing against insulin-induced changes in Ca++ fluxes. Collectively, these results do not support the role of Ca++ as second messenger for insulin action in liver.

Animals↗
PubMed1983

Hepatocyte insulin binding and action in rats with somatomammotrophic tumours.

The effects of chronic elevations of growth hormone levels on hepatic insulin binding and action were studied in rats with subcutaneously implanted growth hormone-producing tumours. These animals were significantly heavier (p less than 0.001; 388 +/- 29 versus 239 +/- 4 g), had elevated insulin levels, (6.8 +/- 0.6 versus 3.3 +/- 0.5 ng/ml), lower glucose concentrations (6.0 +/- 0.4 versus 9.3 +/- 0.5 mmol/l) and larger hepatocyte diameters (28.7 +/- 0.6 versus 24.0 +/- 0.4 micron) and surface areas (2661 +/- 119 versus 1835 +/- 65 micron2) than control rats. Insulin binding and action [net (C14)-glucose incorporation into glycogen] were compared in hepatocytes isolated from these two groups. Because of the difference in hepatocyte size, insulin binding was normalized for cell surface area. Binding of the tracer alone (0.9 +/- 0.05 versus 1.3 +/- 0.12%/cm2) and capacity of the high affinity, low capacity receptor (30.9 +/- 5.9 versus 65.2 +/- 5.9 sites/micron2) were significantly decreased (p less than 0.02) in tumour-bearing rats. Dose-response curves of insulin action in hepatocytes chronically exposed to excess growth hormone were shifted to the right. The maximal response was also significantly decreased. However, the relation between the amount of insulin bound and the proportion of the maximum insulin effect obtained were similar in cells from the two groups. Thus, in rat hepatocytes chronically exposed to excess growth hormone, both a receptor and a post-receptor defect occur while the insulin receptor itself functions normally.

Animals↗
PubMed1982

Persistence of a curvilinear Scatchard plot for insulin binding despite correcting for degradation.

We evaluated whether correcting for insulin degradation products (both cell-associated and those recovered in the media) in the analysis of insulin binding to rat hepatocytes linearized the Scatchard plot. In the presence of bacitracin, the average amount of intact insulin in the cell pellet increased from 68% to 90% and in the media from 21% to 69% when assayed by G-50 Sephadex separation. However, using only the amount of intact insulin in Scatchard analysis still resulted in a curvilinear form whether bacitracin was present or not. Persistence of curvilinear Scatchard plots is probably due to the fact that binding of insulin to hepatocytes in our system is over twice as high as in the cells used in the two studies which reported linearization of the Scatchard plot when these corrections were made. Because of the relatively low binding in those studies, corrections for insulin degradative products resulted in an amount of bound insulin that fell on the initial linear portion of the typical curvilinear Scatchard plot. Bacitracin significantly inhibited insulin degradation and correcting for the amount of insulin degradation in Scatchard analysis does not yield a linear plot.

Animals↗
PubMed1982

Insulin and beta receptor modulation of K homeostasis in nephrectomized dogs with hyperkalemia.

In nephrectomized dogs infused with 2 mEq KCl/kg/hr a homeostatic mechanism retards the development of hyperkalemia by transferring about 70% of the K load to intracellular fluid. beta Adrenergic receptor activity is importantly involved in the transfer process; halting it with propranolol reduces the proportion transferred to less than 35%. The addition of pancreatectomy increases the involvement of beta receptor activity; propranolol treatment now reduces the proportion transferred to less than 20%. Insulin treatment, on the other hand, not only improves transfer of a K load, it also alters the response to propranolol. Nephrectomized dogs treated with 2 U insulin/kg/hr deposit some 80% of the infused K in intracellular fluid. After beta receptor blockade, nearly 90% is transferred. The results suggest that in the K homeostatic mechanism of nephrectomized dogs, insulin and beta receptors may be reciprocally related. K transfer mediated by beta receptors improves after pancreatectomy, and insulin mediated K transfer improves after beta receptors are inactivated.

Aldosterone↗
PubMed1982

Inhibitory effect of a fat-free diet on mammary carcinogenesis in rats.

Young female Sprague-Dawley rats were administered 7,12-dimethylbenz(a)anthracene, and a week later the rats were transferred from commercial feed to a semipurified diet containing 20% corn oil. Eight weeks after receiving the carcinogen, half of the rats were changed to a fat-free diet to determine the effects on mammary tumor growth and development. After another 20 weeks, rats fed the fat-free diet had significantly fewer tumors per tumor-bearing rat and the tumors were smaller than those of rats that continued on the high-fat diet. Rats fed the fat-free diet weighed somewhat less, but showed no physical evidence of essential fatty acid deficiency. Tumors regressed in about half of the rats on the fat-free diet and in some cases became nonpalpable. After 28 weeks on this diet, the remaining rats were transferred back to the high-fat diet and subsequently showed a marked stimulation in tumor growth and development. This continued even after the rats were returned to the fat-free diet 8 weeks later, indicating that the tumors were no longer susceptible to the deprivation of dietary fat. The results of this study provide further evidence that dietary fat affects the promotional stage of mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Insulin binding and action in isolated rat hepatocytes: effect of obesity and fasting.

Insulin binding and action on [14C]glucose incorporation into glycogen were studied in freshly isolated hepatocytes from control, obese, and 48-h fasted-obese rats. Tracer 125I-insulin binding was reduced in the obese animals from 20.8 +/- 1.3% in the controls of 15.9 +/- 0.8% (mean +/- SE). The change in binding was due to a decrease in receptor number with no change in affinity. Fasting the obese animal for 48 h restored the tracer 125I-insulin binding and the receptor number to control levels. Physiologic concentrations of insulin caused an 86% stimulation of net [14C]glucose incorporation into glycogen above the basal level of 9.0 +/- 1.0 nmol incorporated . 10(6) cells-1 . h-1 with an ED50 of 4.0 ng/ml. In obese (greater than 500 g) animals the maximum insulin response measured by percent increase above basal (49%) was reduced, and the ED50 (5.8 ng/ml) was increased. When the obese animals were fasted, the basal and maximum insulin responses were further depressed, but the ED50 was restored to control levels. In conclusion, hepatocytes from obese animals show both a receptor and postreceptor defect. Fasting the animals restores the receptor status to normal, but the postreceptor metabolic defect remains.

Animals↗