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Biomedical subjects

L Doberne

Publications and source records attributed to L Doberne.

10 recordsLinked to original sources
PubMed1984

Does insulin down-regulate its own receptor on erythrocytes in vitro?

The purpose of this study was to examine the in vitro effect of insulin on its own receptors on erythrocytes. Whole blood from 6 fasting normal and 6 diabetic (type II) subjects was incubated without or with exogenous insulin for 5 hours. The insulin binding to erythrocytes was then evaluated. At a tracer concentration, the percent 125I-insulin specifically bound amounted to 8.6 +/- 0.59% and 8.1 +/- 0.41% in fasting normal subjects and type II-diabetics, respectively. In contrast to in vivo studies, supraphysiologic insulin concentrations in the incubation medium did not alter significantly the insulin binding process. Thus, in vitro we could not demonstrate a down regulation of insulin receptor binding. It is likely that factors other than insulin are involved in the short-term regulation of insulin receptor affinity in man.

Erythrocytes↗
PubMed1983

Insulin receptor binding and insulin-mediated glucose uptake in type-II-diabetics.

A 5-hour insulin clamp was performed in 7 normal subjects (N) and 6 type-II-diabetics. After a 10-min-priming insulin infusion, a constant infusion of 1.813 micrograms/m2 s.a./min was given to all subjects. Glycemia was kept at fasting levels by a variable glucose infusion. Under these conditions the amount of metabolized glucose (M) has been calculated and served as a measure of insulin-stimulated glucose disposal. M differed markedly between N (35.6 +/- 3.11 mumol glucose/kg b.w./min and diabetics (17.8 +/- 1.17 mumol glucose/kg b.w./min; p less than 0.01) indicating a diminished insulin sensitivity in the latter group. However, M increased slightly but significantly until the end of the study in both groups. Under fasting conditions the mean percent 125I-insulin specifically bound to 3.5 X 10(9) erythrocytes/ml at tracer concentrations was 12 +/- 1.2% and 8.9 +/- 0.9% in N and diabetics, respectively. During insulin infusion specific insulin binding decreased significantly in both groups by 34% and 41%. Thus, the downregulation of insulin binding was similar in both groups and was due to changes in receptor affinity. Assuming that insulin binding to red blood cells mimic that to target cells we conclude that the cause of reduced glucose utilization in type-II-diabetes lies mainly in changes of postreceptor events rather than in receptor binding.

Adult↗
PubMed1983

Studies of diabetic polyneuropathy using conduction velocity distribution (DCV) analysis.

The distributions of nerve fiber conduction velocities (DCVs) derived from the median nerves of 29 adult diabetic patients (mean age, 52.1 +/- 12.3 years) with mild or no symptoms or signs of polyneuropathy were compared with DCVs from 34 age-appropriate normal subjects. Ten patients (34%) had normal findings (type A DCVs). In the 19 patients (66%) with abnormal DCVs, defined as 10% or more of the DCV area falling outside the normal 95% confidence limits, two distinct patterns of DCV alteration were observed: type B DCVs (11 patients) showed reduced DCVmax, DCVmean, and DCVpeak, together with reduced DCVrange (narrow profile); whereas type C DCVs (8 patients) had reduced DCVmax, DCVmean, DCVpeak, and DCVmin, with normal DCVrange (broad profile). It is proposed that type C DCV represents a more advanced form of type B and that both reflect selective dysfunction of the fastest conducting (presumably largest-diameter) fibers in the nerve trunk. DCVmax was consistently greater than conventional measures of "maximal" CV in all patient subgroups. Patients with abnormal DCVs had higher incidence of mild neuropathic symptoms (15 of 19 versus 4 of 10, p less than 0.01) and greater insulin dependence (11 of 19 versus 1 of 10, p less than 0.001). Serial studies in 10 patients showed, at most, small degrees of change in conduction properties over relatively short intervals (1 to 9 months).

Action Potentials↗
PubMed1982

Effect of age on glucose tolerance, insulin secretion, and in vivo insulin action.

The effect of age on glucose tolerance, insulin secretion, and in vivo insulin action (insulin clamp) was studied in 48 nonobese subjects, all of whom were fully ambulatory and in good general health. The observed age-related increase in fasting plasma glucose (r = 0.35, P less than 0.01) was not due to an increase in relative body weight (RBW). Plasma insulin levels, both fasting and postprandial, tended to rise with age, but these changes were not significant. There was a marginally significant correlation (r = -0.21) between age and insulin-stimulated glucose utilization, which fell to -0.13 when controlled for RBW. However, steady-state insulin levels during the insulin-clamp period were higher in the older subjects, suggesting that age leads to an impairment in insulin catabolism; thus it is likely that the impairment of in vivo insulin action with age was underestimated. The variation in in vivo action between individuals was much greater among the older subjects. It was concluded that the glucose intolerance associated with aging is of relatively minor magnitude when ambulatory, generally healthy, nonobese, and nondiabetic subjects are studied. The cause of the glucose intolerance associated with aging seems to be loss of normal in vivo insulin action. On the other hand, this defect is not shared by all older persons, and in many over the age of 70, glucose transport is as efficient as in persons in their 20s.

Adult↗
PubMed1982

Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin-dependent diabetes mellitus.

The effect of glipizide treatment on diabetic control and on in vivo insulin secretion and action was studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were examined before and after a minimum of 3 mo treatment. Mean (+/- SEM) fasting plasma glucose level fell from 264 +/- 12 mg/dl to 172 +/- 10 mg/dl (P < 0.001) after glipizide treatment, and this was associated with a fall in total plasma glucose response to a test meal of approximately 35%. Mean (+/- SEM) fasting plasma insulin levels increased slightly from 15 +/- 2 micronU/ml following sulfonylurea treatment, and the total plasma insulin response to the test meal increased by 63%. However, there was no correlation (r = - 0.20) between the increase in plasma insulin response and the fall in plasma glucose levels that occurred as the result of sulfonylurea therapy. Glipizide treatment also led to enhanced in vivo insulin action, whether measured by the insulin clamp technique (P < 0.001) or the insulin suppression test (P< 0.02). Furthermore, in this instance there was a significant correlation (r - 0.69, P < 0.001) between the enhanced insulin action and the improvement on diabetes control. Thus, chronic therapy with glipizide, a new sulfonylurea agent, led to increased in vivo insulin secretion and insulin action. These results lend direct support to the assumption that sulfonylurea compounds have a substantial extrapancreatic effect on glucose homeostasis, and suggest that this effect contributes to the therapeutic efficacy of these drugs.

Aged↗
PubMed1982

Comparison of insulin secretion and in vivo insulin action in nonobese and moderately obese individuals with non-insulin-dependent diabetes mellitus.

Insulin secretion and in vivo insulin action were quantified in nonobese and moderately obese patients (approximately 30% overweight) with non-insulin-dependent diabetes mellitus (NIDDM), matched for severity of diabetes. Insulin secretion was assessed by determining plasma insulin responses to a test meal given at noon, and in vivo insulin action by the insulin clamp technique. No significant differences were noted between the two groups for either variable. Thus, it cannot be assumed that the cause of hyperglycemia in patients with NIDDM differs between nonobese and moderately obese subjects.

Blood Glucose↗
PubMed1982

Effect of variations in basal plasma glucose concentration on glucose utilization (M) and metabolic clearance (MCR) rates during insulin clamp studies in patients with non-insulin-dependent diabetes mellitus.

Two insulin clamp studies were performed at different steady-state plasma glucose concentrations in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM). Steady-state plasma insulin concentrations were comparable, with mean +/- SEM levels of 94 +/- 3 and 95 +/- 4 muU/ml being achieved during the two studies. Glucose utilization rate (M) varied directly with plasma glucose concentration in each subject. Thus, the mean +/- SEM value of M was 4.92 +/- 0.73 mg/kg/min when patients were studied at a mean +/- SEM plasma glucose concentration of 226 +/- 15 mg/dl, and M was 2.71 mg/kg/min when the same subjects were studied at a glucose concentration of 118 +/- 6 mg/dl. In contrast, the values for glucose metabolic clearance rate (MCR), which were 2.35 +/- 0.50 and 2.49 +/- 0.47 ml/kg/min, respectively, during the two studies, did not vary significantly with plasma glucose concentration. These data indicate that the glucose metabolic clearance rate (MCR), but not glucose utilization rate (M), can be used to compare in vivo insulin action when insulin clamp studies are performed in subjects with different basal plasma glucose concentrations.

Blood Glucose↗
PubMed1982

Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy.

Plasma lipid concentration and lipoprotein composition were studied before and after several months of glipizide treatment in 23 patients with non-insulin-dependent diabetes mellitus. The mean (+/- SEM) plasma glucose level fell 87 mg/dL, and the fall in plasma glucose concentration was correlated with a reduction in plasma triglyceride, very low-density lipoprotein triglyceride, cholesterol, and low-density lipoprotein cholesterol levels. Furthermore, there was a statistically significant increase in the plasma high-density lipoprotein cholesterol to total cholesterol ratio. Thus, improved diabetic control in patients treated with glipizide with non-insulin-dependent diabetes mellitus leads to changes in lipoprotein metabolism thought to be beneficial in terms of known cardiovascular risk factors.

Aged↗
PubMed1981

Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp.

Insulin resistance was quantified with two different methods in 30 subjects with varying degrees of glucose tolerance. One method, the insulin suppression test, is performed by continuously infusing epinephrine, propranolol, insulin, and glucose. Epinephrine and propranolol suppress endogenous insulin release, and steady-state plasma levels of exogenous insulin and glucose are reached in all individuals. Because the steady-state insulin level is the same in all subjects, the height of the steady-state plasma glucose level provides a direct estimate of insulin resistance. The other method, the euglycemic clamp technique, produces a steady-state level of exogenous hyperinsulinemia by means of a primed and continuous insulin infusion. Glucose is also infused at a rate sufficient to prevent an insulin-induced fall in glucose concentration, and the amount of glucose required to maintain the basal plasma glucose level provides the estimates of insulin resistance. The results indicated that estimates of insulin resistance generated by the two methods were highly correlated (r = 0.93). Furthermore, both methods of assessing insulin resistance indicated that the greater the degree of glucose intolerance, the more severe the insulin resistance. These results serve to further emphasize the importance of insulin resistance in the pathogenesis of hyperglycemia in type II diabetes.

Adult↗