Search PubMed⌕ Search

Biomedical subjects

M B Davidson

Publications and source records attributed to M B Davidson.

At least 127 records · Page 7Linked to original sources
PubMed1982

Diabetes mellitus.

Diabetes mellitus is classified into two major categories: type I, which is insulin dependent, and type II, which is not. Insulin resistance in type II diabetes may be related to impaired receptor binding in some forms of the disorder. In the past, diabetes in pregnant women resulted in high rates of maternal and infant mortality. During the past 10 years, however, better management of maternal diabetes has led to a significant sharp reduction in maternal and fetal morbidity and mortality. The long-term outcome of insulin-dependent diabetes remains gloomy, probably because adequate control of the disease has rarely been achieved. Recently, more stringent efforts have been made to achieve tighter control. Frequent monitoring of blood glucose levels at home and use of constant infusion insulin pumps may help to achieve this end until successful islet transplantation is feasible.

Animals↗
PubMed1981

Insulin binding and action in isolated rat hepatocytes: evidence for spare receptors.

An in vitro assay for insulin action on hepatocytes is described. The 125I-insulin binding and the effects of insulin on net 14C-glucose incorporation into glycogen were studied in suspensions of isolated hepatocytes from fed, 250 gram adult rats. Insulin doubled the basal value (mean +/- SEM) of 9.0 +/- 1.0 nmoles glucose/10(6) cells/hr with a one-half maximal concentration of 3 ng/ml (75 microU/ml) and a maximum effect between 10 and 20 ng/ml (250 microU/ml). Insulin binding was half-maximal at 40 ng/ml and maximal between 100 and 300 ng/ml. Thus, maximal stimulation occurred at approximately 35% of maximum binding implying that hepatocytes have spare receptors for insulin action on net incorporation of 14C-glucose into glycogen. This assay was then used to investigate the time course of activation of insulin action. Isolated hepatocytes were preincubated at 37 degrees C in the presence or absence of 40 ng/ml of insulin for 2, 15, or 30 min, washed, and then tested for action in fresh insulin-free media containing 14C-glucose. No activation was seen after 2 min, a partial activation after 15 min and maximum activation was seen only after a 30 min preincubation. Therefore, insulin activation of glucose incorporation into glycogen in liver is a time-dependent phenomenon that is reversible by early dissociation.

Animals↗
PubMed1981

Autoregulation by glucose of hepatic glucose balance: permissive effect of insulin.

To study the pathways involved and the effect of insulin on the autoregulation of hepatic glucose balance, isolated hepatocytes from normal, diabetic and treated diabetic rats were incubated with varying concentrations of glucose (100-400 mg/dl) with and without pyruvate (10 mM). New glucose production or utilization was calculated from the change in media glucose concentrations before and after incubation, new glycogenolysis by the change in tissue glycogen levels before and after incubation, net glycolysis by following the incorporation of glucose-C14 into lactate C14 and gluconeogenesis by the difference in glucose production in the presence and absence of pyruvate. Hepatocytes from control and insulin-treated animals manifested autoregulation of glucose balance. Glucose modulated the glycogen and glycolytic pathways but did not affect gluconeogenesis. In hepatocytes from diabetic rats, there was no autoregulation, tissue glycogen was unmeasurable both before and after incubation, glycolysis was markedly curtailed and gluconeogenesis was increased. It may be concluded that (1) glucose autoregulates its own production or utilization by modulating the glycogen and glycolytic pathways, (2) autoregulation is lost in severe diabetes leading to fasting hyperglycemia, and (3) insulin has a permissive effect on the autoregulation of glucose balance by maintaining the rate-limiting enzymes, glycogen synthase and glucokinase, so that glucose can exert its effect on these pathways.

Animals↗
PubMed1981

Transmembrane K transfer in hyperkalemic dogs.

In a dog K loaded by infusion of 2 mEq KCl/kg/hr, kaluresis plays a relatively small part in slowing the development of hyperkalemia and cardiotoxicity. These are largely retarded by a non-renal mechanism that transfer most of the infused K from extracellular to intracellular fluid. Treatment with beta receptor blocking dosages of propranolol significantly reduces K transfer capacity, but it also markedly diminishes the KCl stimulated secretory response of insulin, a powerful mediator of K transfer. In dogs in which diminution of the insulin response is prevented by administration of exogenous hormone, beta receptor blockade has no effect on K transfer capacity. Thus, it appears that decreased insulin secretion is responsible for the observed fall of K transfer capacity in dogs with beta receptor blockade. However, other evidence suggests that our results can also mean that a K load elicits the secretion of enough insulin to mediate K transfer in the presence of beta receptor blockade; if the hormone response is absent or deficient, beta receptors may be importantly involved in mediation of K transfer to intracellular fluid.

Animals↗
PubMed1981

Perioperative management of diabetes mellitus.

Hourly plasma glucose concentrations in 191 diabetic patients undergoing 200 operations were measured. The glucose infusion rate was controlled. Insulin-taking diabetics given no insulin or a fraction of their usual dose preoperatively developed rising plasma glucose concentrations beginning with the start of operation. The mean rate was 22 mg.dl-1.h-1 (no insulin) and 17 mg.dl-1.h-1 (one-half to one-fourth the usual dose of insulin). Eight per cent of the patients achieved plasma glucose concentrations greater than 400 mg/dl. Patients given regular insulin during the operation had no hourly rise in plasma glucose. However, hypoglycemia occurred in 5.5 per cent of these patients. The authors suggest that arbitrary management regimens should be abandoned. Plasma glucose levels should be measured frequently and insulin and/or sugar should be given to each patient as needed.

Aged↗
PubMed1979

Alanine metabolism in skeletal muscle in tissue culture.

Alanine production by skeletal muscle in tissue culture was studied using an established myogenic line (L6) of rat skeletal muscle cells. Correlation analyses were performed on rates of metabolism of alanine, glucose, lactate and pyruvate over incubation periods up to 96 h. Alanine production did not correlate significantly with glucose utilization (r = 0.24, P less than 0.20). Alanine production, however, did correlate with lactate production (r = 0.72, P less than 0.0005) as well as medium (r = 0.50, P less than 0.025) and intracellular (r = 0.85, P less than 0.0005) pyruvate concentrations. The intercepts of the latter two correlation analyses indicated that when medium or cell pyruvate fell below 0.28 mM or 1 nmol/mg protein, respectively, net alanine consumption occurred. Alanine synthesis also correlated (r = 0.71, P less than 0.0005) with the percent change in the cell mass action ratio for the sum of the alanine and aspartate aminotransferase reactions, i.e., [alanine] [malate]/[aspartate] [lactate]. These results suggest that alanine production is not necessarily linked to the rate of glucose utilization but rater to pyruvate overflow above a critical intracellular level; under conditions of pyruvate overflow, alanine synthesis is driven by the tendency to establish equilibrium between metabolites of the linked amino acid transaminases in skeletal muscle.

Alanine↗
PubMed1979

The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly.

There seems little doubt that the disposal of a glucose load is progressively impaired during aging. The mechanism(s) for this alteration remains unclear. Five possibilities have been raised: (1) poor diet, (2) physical inactivity, (3) decreased lean body mass in which to store the carbohydrate load, (4) decreased insulin secretion, and (5) insulin antagonism. Although poor diet and physical inactivity may contribute to some of the abnormal glucose tolerance tests of the older population, these two factors do not provide a full explanation. Diminished lean body mass may play some role but there is almost certainly an additional effect due to aging. A few papers have suggested that glucose-induced insulin secretion may be impaired as the population ages, but the bulk of studies in this area conclude that normal or increased amounts of insulin are released by the pancreatic beta-cell during aging. If abnormalities of insulin secretion exist, either in degree or timing, they are subtle and would not seem sufficient to account for the great number of older subjects who manifest impaired glucose tolerance. The evidence for insulin antagonism seems the strongest but the data are certainly not conclusive. In actuality, the aging effect on carbohydrate metabolism may be heterogeneous in nature. Either some or all of these five factors may contribute to the aging effect to varying degrees in individual subjects. Alternatively, the glucose intolerance of aging may represent a heterogeneous group of disorders. In any event, until better methods to identify possible subgroups of these subjects and/or a marker for diabetes mellitus independent of glucose concentration become available, this problem will remain difficult to resolve. Based on the currently available data, it seems prudent to diagnose diabetes mellitus only if fasting hyperglycemia is present.

Aged↗
PubMed1979

Insulin antagonism in cultured rat myoblasts secondary to chronic exposure to insulin.

Rat myoblasts grown in culture for 5 days responded acutely to insulin (10 mU/ml) over a 3 hour incubation period by stimulating C14-glucose incorporation into glycogen by 260%. When these cells were grown in the presence of insulin (10 mU/ml) for the first 4 days (no exposure to insulin during the final 24 hours), insulin had no significant acute effect. These data provide direct evidence that insulation itself may induce antagonism under certain conditions.

Animals↗