Reduced Plasma Glucose Levels Research Articles

Beta-hydroxybutyrate reverses insulin-induced hypoglycemic coma in suckling-weanling mice despite low blood and brain glucose levels.

In normal suckling-weanling mice, DL-beta-hydroxybutyrate (30 mmol/kg ip) stimulated insulin secretion and reduced plasma glucose levels. In the brains of these animals, glucose levels were tripled due to a reduced rate of glucose utilization (determined by deoxyglucose phosphorylation). Other metabolite changes were compatible with inhibition of hexokinase, phosphofructokinase, glyceraldehyde-P-dehydrogenase, and pyruvate dehydrogenase activities. In contrast to the decrease in cerebral glycolysis, metabolite changes were compatible with an increase in the Krebs citric acid metabolic flux. The brain energy charge was also elevated. While it is generally believed that ketone bodies cannot sustain normal brain metabolism and function in the absence of glucose, DL-beta-hydroxybutyrate (20 or 30 mmol/kg ip) reversed insulin (100 U/kg sc)-induced hypoglycemia despite the persistence of a critically reduced plasma glucose concentration and near-zero brain glucose levels. Metabolic correlates of possible significance in the behavioral recovery from coma were reductions of the elevated levels of brain aspartate to below normal and ammonia levels to normal. Levels of acetyl CoA were unchanged both before and after treatment with beta-hydroxybutyrate.

Differential effects of insulin on brain monoamine metabolism in rats.

The effect of a subconvulsive dose of insulin, which caused a 70% reduction of plasma glucose levels, on catecholamine and 5-hydroxytryptamine turnover in different brain regions of rats was investigated. The turnover of norepinephrine was found to be increased in the hemispheres and that of 5-hydroxytryptamine was increased in the limbic forebrain and hemispheres, whereas the dopamine turnover was decreased in the striatum and limbic forebrain.

Modulation of basal insulin secretion in the obese, hyperglycemic mouse

The modulation of basal insulin secretion in vivo in the obese hyperglycemic, hyperinsulinemic ob ob mouse was investigated by recording the plasma insulin and glucose levels during 2 hr after administration of various insulin secretory modifiers assumed to interfere with different regulatory mechanisms for insulin release. Normal, lean NMRI mice served as controls. Glucose sensitive mechanisms were tested by studying the effects of mannoheptulose. It was observed that mannoheptulose induced a marked hyperglycemia of comparable magnitude in both obese and lean mice. However, it exerted a more profound and sustained inhibitory effect on insulin secretion in the obese mouse than in the lean control animals, suppressing the insulinogenic index by 85%–90% in the obese animals from 30 min and onwards. Autonomic regulation was studied by means of receptor blockade. β-Adrenoceptor blockade by l-propranolol transiently inhibited basal insulin secretion in both obese and lean animals by a maximum of about 40%, the depression in obese animals being somewhat more sustained. Further, in both types of mice, α-adrenoceptor blockade by phentolamine induced a sustained elevation of plasma insulin levels to about 200% over control values. Thus no impressive abnormality in the adrenergic regulation of insulin secretion in the obese mouse was detected. Cholinergic blockade by methylatropine was found to induce a pronounced and sustained reduction of plasma insulin levels of about 60% in the obese mouse whereas the lean mice exhibited only a slight and transitory depression. The islet hormone, pancreatic polypeptide (PP) was observed to induce a slight short-lasting depression, about 35%, of basal insulin levels in both obese and lean mice concomitant with a slight reduction in plasma glucose levels. Vinblastine, in a dose known to induce a 75% reduction of the amount of microtubules in the insulin cells, was found to depress basal insulin secretion in the obese mouse by about 60% from 30 min and onwards, whereas only a slight slow-onset depression of about 25% was noted in the lean mouse. A slight hyperglycemia was noted in lean but not in obese mice. It is concluded that the basal hypersecretion of insulin in the obese mouse is of multifactorial origin. Fully established it probably is largely governed by an increased sensitivity and reactivity to glucose stimulation and to an enhanced responsiveness to a normal and/or increased vagal activity.

Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice.

Obese (ob/ob) and diabetes (db/db) mice are genetic mutants that have been shown to have altered levels of central catecholamines as well as syndromes of obesity, hyperphagia, and hyperglycemia. Because of catecholamines, and particularly norepinephrine (NE), are implicated in the control of feeding, levels of central catecholamines were experimentally reduced in ob/ob and db/db mice to investigate the role of the catecholamines in these cases of spontaneously occurring obesity. Lesions produced by 6-hydroxydopamine (6-OHDA) were used to produce large depletions of NE and dopamine (DA) in both ob/ob and db/db mice and in lean control mice of the same background strains. In the db/db but not the ob/ob, central catecholamine depletion was accompanied by a significant and persistent weight loss and by a reduction in plasma glucose levels when compared with vehicle-infused controls. Treatment with the NE uptake blocker desmethylimipramine (DMI) prior to 6-OHDA infusions attenuated NE but not DA depletion. Diabetes mice that received DMI pretreatment showed a weight loss and decrease in plasma glucose proportional to the amount of NE depletion. Lean mice that received the 6-OHDA treatments showed only a transient weight loss and no significant change in blood glucose. It is concluded that abnormalities in central noradrenergic systems may account for part of the obesity syndrome observed in the diabetes mouse.

DIABETES: THE QUEST FOR BASAL NORMOGLYCÆMIA

Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy. Many patients who are thought to be controlled by diet alone continue to have high plasma-glucose levels. As the rise in the basal plasma-glucose concentration is the predominant glucose abnormality of diabetes, treatment should be aimed primarily at producing basal normoglycæmia. 18 mild, maturity onset diabetics have been treated with a basal insulin supplement provided by single daily injections of insulin zinc suspension (crystalline) 'Ultralente'. Overnight basal normoglycæmia has been obtained with markedly reduced plasma-glucose levels during the day. Plasma-triglyceride levels have become normal in most patients. The required insulin dose need not be determined empirically, but can be calculated from the basal plasma-glucose level and the degree of obesity. There is minimum risk of hypoglycæmia, and rigid dietary restriction is unnecessary. As mild diabetics are prone to complications, treatment with basal insulin supplements may be beneficial when diet alone fails to produce basal normoglycæmia.

The in vivo metabolism of 14C-glucose and 14C-glycine in insulin-treated northern pike ( Esox lucius L.)

The effects of codfish insulin (2 IU/kg) on 14C-glucose and 14C-glycine metabolism in vivo were studied in cannulated Northern pike ( Esox lucius L.). Insulin significantly reduced plasma glucose levels and increased the incorporation of 14C-glucose carbon into liver and muscle lipid and muscle protein, and of 14C-glycine carbon into muscle protein. These results suggest that the metabolic role of insulin in pike is similar to that observed in mammals.

Pharmacodynamic aspects of two sulphonylurea derivatives glipizide and glibenclamide

The results of experiments in dogs with and without two glucose loads and in the isolated pancreas to compare the pharmacodynamics of two low-dosage aryl-sulphonylureas, glipizide and glibenclamide, are described and discussed. — The results agree with those obtained by other authors confirming that glibenclamide shows delayed but prolonged activity on both plasma insulin and glucose levels. Moreover glibenclamide counteracts the hyperglycaemia induced by the second glucose load less efficently. Glipizide acts faster on insulin and glucose levels, which return quickly to normal. When a second glucose load was given it was still more active in reducing plasma glucose levels. The dynamics of insulin secretion following glipizide more closely resembles tolbutamide than glibenclamide.

Pharmacological Evaluation of 3,4-Dimethoxyphenylacetamide

Studies on the pharmacological activity of 3,4-dimethoxyphenylacetamide revealed that the compound produced definite signs of CNS depression. A hypocholesterolemic effect was also demonstrated, plus tendencies toward a reduction in plasma glucose levels.