Post-glucose Insulin Research Articles

Effect of starvation on hepatic glycogen metabolism and glucose homeostasis

The effects of starvation on the hepatic glycogen synthase and phosphorylase systems were sequentially assessed in fed and 24–120-hr-fasted rats. Enzymic changes before and after glucose were correlated with simultaneous measurements of hepatic cyclic AMP and glycogen concentrations and glucose, insulin, and glucagon concentrations in the portal vein plasma. Fasting caused parallel changes in plasma glucose and hepatic glycogen concentrations with decreases by 24 hr and subsequent increases, which correlated with increases in hepatic synthase I and decreases in phosphorylase activities. Hepatic cyclic AMP levels increased at 24–48 hr, decreased below fed levels at 96 hr, and increased again at 120 hr. Fasting caused progressive impairment of glucose disposal, decreased basal and postglucose insulin concentrations, and decreased basal glucagon levels at 48–72 hr. Hepatic synthase I increments following glucose were exaggerated in 48–120-hr-fasted rats, although consistent phosphorylase decrements were seen only in fed rats. There was no clearcut relationship between synthase activation and phosphorylase inactivation following glucose in fed or fasted rats.

Insulin Response to Glucose and Tolbutamide in “Essential” versus “Pancreatic” Mild Glucose Intolerance

In order to determine whether the symptom of “mild glucose intolerance” is associated with functional β cell abnormalities, differing depending on their etiology, the insulin response to intravenously injected glucose was compared with that to intravenous tolbutamide in three homogeneous groups of subjects. Normal weight (NW) subjects comprised one group; chronic pancreatitis (CP) patients'another and obese subjects (O) the other. Each group included both nondiabetic and chemical diabetic subjects. A. In nondiabetic subjects the early insulin response to glucose (0-10' post glucose insulin area) was similar to that to tolbutamide (NW:310N/ml. x mn. versus 343-CP:299 versus 318-O:576 versus 600). B. In all the diabetics the early insulin response to glucose was diminished compared to their nondiabetic counterparts (NW:114 versus 310; CP:120 versus 299; O:320 versus 576. C. The early response to tolbutamide, compared with that of their nondiabetic counterparts, was similar for the diabetic subjects in the normal-weight (333 to 343 for the controls) and overweight, having or not having a family history of diabetes, (779 and 752 respectively to 600) groups but lower for the diabetics in the chronic pancreatitis group (120 to 318). While in the chemical diabetes of chronic pancreatitis patients the lower response to glucose seems due to a reduction in the functional mass of the cells, in essential diabetes of normal weight as well as obese subjects it is related to an insensitivity of the pancreas to glucose. Estimation of the latter by comparison with the response to tolbutamide in a given individual allows one to dispense with the necessity of referring to a control group and to eliminate the influence of hyperinsulinism.

Studies of glucose, insulin, and lipid metabolism in amyotrophic lateral sclerosis and other neuromuscular disorders.

Abstract Inpatients with amyotrophic lateral sclerosis (ALS) and with other various neuromascular (NM) diseases were compared in their responses to the intravenous glucose tolerance test (GTT), the insulin tolerance test (ITT), and the tolbutamide tolerance test: (TTT). Patients with neuromuscular diseases other than ALS (NM control group) responded for all studies within the normal range. Higher fasting serum lipid levels but no significant differences in fasting serum glucose, insulin, or human growth hormone (HGH) were noted in the ALS group. Lower rates of glucose utilization and higher post-glucose insulin levels during the intravenous GTT were observed in the ALS group. These and similar results from the TTT were interpreted as resistance to endogenous insulin in ALS. The ITT studies showed a similar resistance to exogenous insulin among the ALS patients. There was no relationships among the metabolic abnormalities and clinical state of the ALS patients. These data show that ALS patients have insulin resistance and decreased glucose utilization which cannot be explained purely by muscular dysfunction, other adventitious factors secondary to this motor neuron disease, or pancreatic dysfunction. These metabolic abnormalities associated with ALS are differentiated from those of late-onset diabetes, obesity, inanition, and myotonic dystrophy but not from those of severe depression.

Diabetes in the Seneca Indians. Plasma insulin responses to oral carbohydrate.

In a group of adult Seneca Indians living in Western New York, 14 per cent were discovered to have previously diagnosed diabetes, and 20 per cent of the remainder had a plasma glucose of 200 mg. per 100 ml. or greater one hour after oral carbohydrate. This report describes the glucose and insulin responses to oral carbohydrate in fifty of these subjects who were not previously known to have diabetes during initial testing. On the basis of the results of a two-hour oral glucose tolerance test, forty-six subjects were classified into “diabetic” or “normal” categories. Four persons formed an intermediate group. The diabetics differed from the normals in that (1) they were older and more obese, though even the normal population was significantly obese, and (2) the mean fasting plasma insulin level was three times greater and the insulin response to oral glucose two and one-half times greater than in normals. When diabetics were subdivided on the basis of obesity or degree of glucose intolerance, no significant differences in insulin secretion could be detected. A group of diabetic subjects with a degree of obesity comparable to that of normal subjects still demonstrated two-fold increases in both fasting and postglucose insulin levels. The elevated insulin levels of diabetics can be explained only in part by co-existent obesity and suggest the presence of insulin resistance associated with diabetes in these Indians.

Effects of hypokalemia on carbohydrate and lipid metabolism in the rat.

A study has been made of the effect of hypokalemia on carbohydrate and lipidmetabolism. Forty-two male Wistar rats, divided into three groups, were fed a low-potassium diet for two weeks. One group was injected with saline and fed a diet and drinking water supplemented with potassium, a second group was injected with desoxycorticosterone acetate (DOCA), while the third group was DOCA-treated and given potassium supplement. One week after the last injection, intracardiac glucose tolerance tests were performed, and blood and tissue specimens obtained for potassium, insulin, glucose, free fatty acids (FFA), and glycogen. Hypokalemia, successfully induced by this regimen, was associated with: (1) retardation of growth; (2) increased liver and muscle glycogen; (3) no change in liver potassium; (4) increased fat potassium; (5) decreased muscle potassium; (6) elevation of fasting, and one- and two-hour post-glucose blood sugar concentrations; (7) no change in rate of early rapid disappearance of injected glucose; (8) no effect on fasting or post-glucose plasma FFA levels; and (9) no effect on mean fasting or post-glucose insulin levels, but a reduction in differential insulin response after glucose.