Reduced Blood Glucose Concentrations Research Articles

Blood glucose control and lipolysis in diabetes mellitus.

The relationship between the blood glucose level and the rate of lipolysis was investigated in 19 maturity onset diabetics (MOD) and 9 juvenile onset diabetics (JOD). Subcutaneous adipose tissue was incubated with and without isoprenaline or noradrenaline. Before antidiabetic treatment the blood glucose concentration was positively correlated with basal and catecholamine-induced rates of lipolysis in MOD (R = 0.41--0.60) and in JOD (r = 0.51--0.71). The reduction in blood glucose concentration during antidiabetic treatment was positively correlated with the reduction in the rate of lipolysis in MOD (r = 0.50--0.64) and in JOD (r = 0.75--0.90). Fat cell size and blood glucose level were not correlated either in untreated or treated diabetics. In diabetes mellitus, blood glucose homeostasis and rate of lipolysis in adipose tissue seem to be associated. The relationship is most apparent in JOD.

Effect of somatostatin suppression of glucagon secretion on glucose production in sheep.

The effect of somatostatin (SRIF) on glucagon and insulin secretion was examined in fed and fasted sheep. This was related to changes in glucose production. Infusion of SRIF at 80 micrograms/h caused a marked reduction in plasma glucagon concentrations. However, the insulin response to SRIF infusion was not consistent; its concentrations decreased occasionally, but often did not change. The depression of glucagon was not associated with a significant reduction in blood glucose concentrations in either fed or fasted sheep, but was associated with a reduction in glucose production by 12--15%. The inhibitory effect of insulin on glucose production was not markedly increased by glucagon deficiency. Infusion of insulin at 1.17 U/h with SRIF decreased glucose production only an additional 10%. Thus, it appears that under basal conditions pancreatic hormonal influences on hepatic glucose production were relatively small in sheep. This implies that under normal conditions in sheep, substrate supply has a much greater impact on hepatic glucogenesis than do hormones.

The regulation of gluconeogenesis by diet and insulin in rainbow trout (Salmo gairdneri).

1. The effects of diet composition and insulin treatment on blood glucose level, blood amino acid concentrations, the activities of two hepatic gluconeogenic enzymes (fructose diphosphatase,EC3.1.3.11; phosphoenolpyruvate carboxykinase,EC4.1.1.32) and of two hepatic glycolytic enzymes (hexokinase,EC2.7.1.1; pyruvate kinase,EC2.7.1.40) were examined in rainbow trout (Salmo gairdneri).2. Blood glucose levels were much higher in trout given a high-carbohydrate (HC) diet than in those given a high-protein (HP) diet. Insulin reduced blood glucose concentration in the HC-fed fish but had no effect in HP-fed fish.3. Plasma amino acid concentrations were higher in HP-fed trout than in HC-fed trout. Insulin reduced plasma amino acid levels in both groups.4. Gluconeogenic enzyme activities were higher in HP-fed trout than in HC-fed trout. Insulin reduced phosphoenolpyruvate carboxykinase activity in HP-fed trout but had no effect on either enzyme activity in the HC-fed trout.5. Pyruvate kinase activity was greater in HC-fed trout than in HP-fed trout. Insulin did not affect pyruvate kinase activity in the HC-fed trout but reduced it in HP-fed trout.6. Hexokinase activity was not affected by the diet treatments used, but was enhanced in the trout treated with insulin. Glucokinase (EC2.7.1.2) was not detected in any of the trout livers.7. The results suggest that the inability of trout to control blood glucose concentration is partly due to a lack of glucose-phosphorylating capacity. Gluconeogenesis is controlled in response to diet and insulin by changes in enzyme level and by variation in concentration of gluconeogenic substrates.

Ethanol effects of substrate utilization by the human brain

Arterial concentrations and arterio-jugular vein differences of ethanol, acetate, glucose, lactate, pyruvate, glycerol, free fatty acids and ketone bodies were determined in seven healthy male volunteers before and during an infusion of ethanol, which gave a blood alcohol concentration of about 12 mmol/l. Arterial-jugular vein (A-JV) oxygen differences were unchanged throughout the study. Ethanol caused a small reduction in blood glucose concentration, from a mean of 5.1 to 4.7 mmol/l, and the A-JV difference fell significantly. When alcohol was given, arterial acetate concentration rose quickly to about 1 mmol/l and was unchanged thereafter. All subjects had a positive arterio-venous difference for acetate. Arterial lactate concentration was doubled by ethanol and the normal release from the brain was abolished. Arterial alanine concentration decreased significantly, from 0.19 to 0.16 mmol, when alcohol was given but no net exchange by the brain could be observed. It is concluded that: (a) acetate can be taken up by the brain and if totally oxidized, could account for 6% of the oxygen consumption; (b) glucose arterial-jugular vein difference is decreased by ethanol, suggesting an attenuation in glucose uptake; and (c) lactate net release is abolished by alcohol, probably due to the increased arterial concentration.

Ethanol effects of substrate utilization by the human brain

Arterial concentrations and arterio-jugular vein differences of ethanol, acetate, glucose, lactate, pyruvate, glycerol, free fatty acids and ketone bodies were determined in seven healthy male volunteers before and during an infusion of ethanol, which gave a blood alcohol concentration of about 12 mmol/l. Arterial-jugular vein (A-JV) oxygen differences were unchanged throughout the study. Ethanol caused a small reduction in blood glucose concentration, from a mean of 5.1 to 4.7 mmol/l, and the A-JV difference fell significantly. When alcohol was given, arterial acetate concentration rose quickly to about 1 mmol/l and was unchanged thereafter. All subjects had a positive arterio-venous difference for acetate. Arterial lactate concentration was doubled by ethanol and the normal release from the brain was abolished. Arterial alanine concentration decreased significantly, from 0.19 to 0.16 mmol, when alcohol was given but no net exchange by the brain could be observed. It is concluded that: (a) acetate can be taken up by the brain and if totally oxidized, could account for 6% of the oxygen consumption; (b) glucose arterial-jugular vein difference is decreased by ethanol, suggesting an attenuation in glucose uptake; and (c) lactate net release is abolished by alcohol, probably due to the increased arterial concentration.

Long term treatment of moderate hypertension with penbutolol (Hoe 893d). II. Effect on the response of plasma catecholamines and plasma renin activity to insulin-induced hypoglycemia.

The effect of insulin-induced hypoglycemia on the blood levels of catecholamines and renin activity has been studied in five patients with moderate hypertension before and after treatment for 3 - 8 months with penbutolol (PEN) 20 - 30 mg twice daily. Penbutolol caused no change in fasting blood glucose level. Insulin o.1 IU per kg body weight i.v. reduced blood glucose concentration by approximately 50 per cent after 30 - 45 min, both before and during treatment with penbutolol. Hypoglycemia prior to medication was accompanied by a marked increase in the production of adrenaline and a minor increase of noradrenaline in all five patients. During treatment the response of adrenaline to hypoglycemia was reduced in four patients and the data was inconclusive in one. Basal renin activity was rather low in three patients, within the normal range in one and relatively high in one. Before penbutolol the hypoglycemia-induced increase in catecholamine production caused no change in plasma renin activity in the three patients with low basal levels, whereas a marked increase was observed in the other two. During medication plasma renin activity remained unchanged on induction of hypoglycemia regardless of the catecholamine response. Despite the marked increase in plasma adrenaline following insulin-induced hypoglycemia, no statistically significant increase in pulse rate was recorded.

Endogenous and Exogenous Insulin Responses in Patients With Cystic Fibrosis

Eight male patients with cystic fibrosis, normal nutrition, normal physical activity, relatively mild pulmonary disease, no evidence of liver disease and no family history of diabetes mellitus underwent a series of carbohydrate tolerance tests in comparison with a group of 18 normal male subjects matched for age and body weight. Compared with the normal group, the patients with cystic fibrosis had significantly impaired glucose tolerance and significantly lower serum immunoreactive insulin levels during oral and intravenous glucose tolerance tests; serum insulin levels were also significantly lower after intravenous administration of tolbutamide in the patients with cystic fibrosis, but the reduction in blood glucose concentration in each group was not significantly different. During an intravenous insulin test, the decrease in blood glucose concentration was the same for both groups, in spite of significantly lower serum insulin levels in the patients with cystic fibrosis .The percentage fall in plasma free fatty acids was at least as great in the patients with cystic fibrosis as in normals during the test procedures; while a significant decrease in plasma alpha-amino nitrogen after intravenously administered insulin was seen only in the patients with cystic fibrosis. These studies suggest that the carbohydrate intolerance of cystic fibrosis is consequent upon an impaired insulin response to glucose, but that this insulin deficiency is partly compensated for by increased peripheral tissue sensitivity to insulin.

Plasma alanine: Relation to plasma glucose, glucagon, and insulin in the neonate

An attempt was made to determine if correlations exist among plasma concentrations of alanine, the major amino acid substrate for gluconeogenesis, and plasma concentrations of glucose, glucagon, and insulin in normal newborn infants. The effects of an intravenous infusion of cl-alanine (1 mMl/kg) to six neonates was also determined. Although a peak in alanine concentration coincided with a nadir in glucose concentration at 12 hours of life, no correlation existed between the observed changes in alanine and glucose, or alanine and glucagon. Infused alanine caused increases in both plasma glucose and glucagon concentrations, as in the adult; the responses, however, were of small magnitude. Our data indicate that reduced blood glucose concentrations in the normal newborn infant are not due to a deficiency of alanine substrate for gluconeogenesis. And, although alanine stimulates secretion of glucagon, there is no consistent correlation between plasma alanine and glucose, or plasma alanine and glucagon concentrations during the early neonatal period. thus the key factors in control of glucose concentrations in the newborn period cannot be deduced from simple relationships of these plasma constituents.

THE CRITICALLY ILL CHILD: HYPOGLYCEMIA

HYPOGLYCEMIA represents a significant emergency situation in pediatrics. Although recent studies indicate that cerebral tissue can utilize substrates other than glucose, cose, especially in the newborn period and during prolonged fasting,1 no substrate can successfully correct the neurophysiologic sequellae of glucose deprivation on the central nervous system. Since permanent neurological effects of hypoglycemia correlate with the duration of time that cerebral tissue is deprived of glucose, early recognition and treatment of hypoglycemia is essential. The diagnosis of hypoglycemia obviously depends on demonstration of a significant reduction in blood glucose concentration. Diagnostic criteria, similar to those developed by Cornblath and Schwartz,2 have been widely accepted: two or more blood glucose values of less than 30 mg/100 ml in full-term infants; concentration of blood glucose less than 20 mg/100 ml in the neonate weighing less than 2,500 gm; blood glucose values of less than 40 mg/100 ml in the older infant and child. Since hypoglycemia is defined in terms of the concentration of blood glucose, it is essential to utilize analytic methods which are specific for glucose. The most common method utilizes glucose oxidase, although other methods provide appropriate specificity. A rapid modification of the glucose oxidase method is represented by Dextrostix,* although accurate application of this diagnostic aid to hypoglycemia requires considerable training and experience.3 Recently, a modification of the Dextrostix method has been reported, enabling reproducible measurement of values in the range of 20 to 40 mg/100 ml.4 Confirmation of results obtained by Dextrostix with reliable laboratory methods should be effected upon recognition of hypoglycemia.

Studies in the diabetic mutant mouse. V. Glucose tolerance in mice homozygous and heterozygous for the diabetes (db) gene.

Mice homozygous and heterozygous for the diabetes (db) gene were studied to determine: 1. whether latent carbohydrate intolerance is present in young normoglycemic diabetic mutants (db/db); 2. whether normoglycemic food restricted diabetic mutants are carbohydrate intolerant; and 3. whether mice heterozygous for thedb gene (db/+) manifest abnormalities in glucose tolerance, serum IRI levels or body weights. Blood glucose levels were determined 0, 1/2, 1, 2 and 3 h following intraperitoneal administration of 2 mg glucose/g body weight. Normals (+/+) and diabetics (db/db) showed similar glucose tolerance curves during the first two weeks of life; however, both were markedly glucose intolerant compared to normal adult mice. At 3 weeks a small number of mutants had higher 3 h levels than any achieved in normal mice. By 4 weeks the average value for diabetics prior to glucose loading (0 time) was significantly (P < 0.02) elevated (db/db — 144 mg glucose/100 ml, +/+ = 124 mg glucose/100 ml). Although food restriction reduced blood glucose concentration at 0 time, persistence of carbohydrate intolerance was readily demonstrable following glucose loading. — Abnormalities in heterozygotes (db/+), 3 to 16 months of age, were primarily restricted to male mice, which showed moderate, but statistically significant elevations in blood glucose both at 0 time and following glucose administration. Forty percent of male heterozygotes had higher serum IRI levels than any observed in normal control males. Body weights of male heterozygotes were significantly greater (P<0.01) than those in agematched normals.