Plasma glucose and insulin responses to oral and intravenous glucose in cold-exposed humans

Although glucose tolerance and skeletal muscle glucose uptake are markedly improved by cold exposure in animals, little is known about such responses in humans. This study used two variations of a glucose tolerance test (GTT) to investigate changes in carbohydrate metabolism in healthy males during nude exposure to cold. In experiment 1, an oral GTT was performed in the cold and in the warm (3 h at 10 or 29 degrees C). To bypass the gastrointestinal tract, and to suppress hepatic glucose output, a second experiment was carried out as described above, using an intravenous GTT. Even though cold exposure raised metabolic rate greater than 2.5 times, plasma glucose and insulin responses to an oral GTT remained unaltered. In contrast, cold exposure reduced the entire plasma glucose profile as a function of time during the intravenous GTT (P less than 0.05), as plasma glucose was returned to basal levels within 1 h in comparison to a full 2 h in the warm, despite low insulin levels. The results of the intravenous GTT demonstrate that even with low insulin levels, carbohydrate metabolism is increased in cold-exposed males. This effect could be masked in the oral GTT by gastrointestinal factors and a high hepatic glucose output. Cold exposure may enhance insulin sensitivity and/or responsiveness for glucose uptake, mainly in shivering skeletal muscles.     

Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice.

In this study, we examined glucose homeostasis and insulin secretion in transgenic mice overexpressing the human apolipoprotein CIII gene (apo CIII tg). These mice have elevated plasma levels of triglycerides, FFA and cholesterol compared to control mice. The body weight, plasma glucose, and insulin levels, glucose disappearance rates, areas under the ipGTT curve for adult (4 - 8 mo. old) and aged (20 - 24 mo. old) apo CIII tg mice and the determination of insulin during the ipGTT were not different from those of control mice. However, an additional elevation of plasma FFA by treatment with heparin for 2 - 4 h impaired the ipGTT responses in apo CIII tg mice compared to saline-treated mice. The glucose disappearance rate in heparin-treated transgenic mice was slightly lower than in heparin-treated controls. Glucose (22.2 mmol/l) stimulated insulin secretion in isolated islets to the same extent in saline-treated control and apo CIII tg mice. In islets from heparin-treated apo CIII tg mice, the insulin secretion at 2.8 and 22.2 mmol glucose/l was lower than in heparin-treated control mice. In conclusion, hypertriglyceridemia per se or a mild elevation in FFA did not affect insulin secretion or insulin resistance in adult or aged apo CIII tg mice. Nonetheless, an additional elevation of FFA induced by heparin in hypertriglyceridemic mice impaired the ipGTT by reducing insulin secretion.     

Blood glucose and insulin levels in thymectomized rats.

The rise of blood glucose level under sugar load was much greater in thymectomized than in normal rats, whereas the insulin level remained practically unchanged. This suggests that the rise of blood sugar level is due to two factors, one being the accumulation in blood of a substance, corresponding to the blood glucose level stimulator stored in the thymus, the other the simultaneous inhibition of insulin production, or of insulin transport, into blood.     

Size at birth, fasting glucose and insulin levels and insulin resistance in adult twins.

Studies in singletons have found an association between birthweight and Type 2 diabetes in adult life. The aim of this study was to investigate whether this association could also be seen in twins. 59 monozygotic (MZ) and 69 dizygotic (DZ) same-sex twin pairs aged 19-50 years and 89 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from a local obstetric database. Associations between adult glucose, HbA(1)C and insulin levels and insulin resistance and birthweight were assessed by linear regression with adjustment for confounding variables. Twins were significantly lighter at birth than singleton controls, but there were no significant differences in adult weight, glucose, HbA(1)C and insulin levels or insulin resistance between twins and controls. The relationship between birthweight and fasting glucose and insulin levels, and insulin resistance was not significantly different from zero in either twins or controls, but birthweight was significantly negatively associated with HbA(1)C only in controls. There was no evidence of a difference between MZ and DZ twins in unpaired or within-pair analysis. These results provide little evidence that low birthweight in twins increases the risk of impaired glucose-insulin metabolism in young adults or that genetic factors can account for the association observed in singletons.     

Plasma tumor necrosis factor-alpha levels and insulin resistance in nondiabetic hypertensive subjects

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is associated with insulin resistance in certain conditions. However, whether TNF-alpha is related to insulin resistance in hypertensive subjects is still controversial. The aim of this study was to determine the status of TNF-alpha and insulin resistance in hypertension. METHODS: Newly diagnosed nondiabetic 17 essentially hypertensive (6 men, 11 women) patients, and 11 control healthy subjects (5 men, 6 women) are involved in the study. Body mass index (BMI), insulin, fasting blood glucose, cholesterol, triglyceride, and TNF-alpha levels were measured. Insulin resistance is assessed according to homeostasis model of assessment (HOMA-IR). RESULTS: Serum insulin (8.4 +/- 2.7 vs. 6.1 +/- 1.4 mIU/ml; p < 0.01), triglyceride (245.0 +/- 39.9 vs. 193.0 +/- 22.8 mg/dl; p < 0.01), and TNF-alpha (4.2 +/- 0.7 vs. 3.0 +/- 0.6 pg/ml; p < 0.001) levels, and HOMA-IR (2.0 +/- 0.8 vs. 1.3 +/- 0.3; p < 0.001) were significantly higher in the hypertensive patients compared to the normotensive control group. There were positive correlations between TNF-alpha levels and body mass index (r = 0.64, p < 0.01), and triglyceride (r = 0.55 p = 0.02) levels in the whole study group. However, there was no correlation of either TNF-alpha or HOMA-IR. CONCLUSIONS: Our data revealed that hypertensive patients have insulin resistance and higher TNF-alpha levels, but there is no relation between TNF-alpha levels and insulin resistance.     

Effect of high levels of insulin on glucose utilization and glucose production in pregnant and nonpregnant sheep

The present study was conducted to test the hypothesis that pregnancy in sheep alters the effects of insulin on glucose utilization and glucose production. Euglycemic, hyperinsulinemic glucose clamp experiments were performed in chronically catheterized, unstressed, fed or 24-hr fasted, nonpregnant sheep and fed, pregnant sheep. Endogenous glucose production rate for the whole sheep and glucose utilization rate of the uterine and nonuterine maternal tissues were measured in control and high-insulin periods by tracer technique using [6-3H]glucose. Control glucose utilization rate in the fed, nonpregnant sheep was significantly (P less than 0.05) greater than that in the fasted, nonpregnant sheep, 2.29 +/- 0.17 and 1.86 +/- 0.11 mg/min/kg, respectively, and also in the nonuterine maternal tissues of the pregnant sheep (1.71 +/- 0.18 mg/min/kg). Insulin stimulated glucose utilization 116.4 +/- 14.8% in the fed, nonpregnant sheep but only 82.8 +/- 11.0% in the fasted, nonpregnant sheep and 94.2 +/- 14.3% in the nonuterine tissues of the fed, pregnant sheep. Also, insulin suppressed endogenous glucose production to 53.2 +/- 5.6% in the fed, nonpregnant sheep, to 3.9 +/- 3.1% in the fasted, nonpregnant sheep, and to 9.0 +/- 3.7% in the fed, pregnant sheep. In the pregnant animals, uterine glucose uptake and uterine glucose utilization were not different and were not altered by changes in maternal insulin concentration. The results indicate that during late pregnancy glucose utilization is reduced and resistance to the effect of insulin to enhance glucose utilization is present in the nonuterine maternal tissues compared with nonpregnant, fed sheep. In contrast, the effectiveness of insulin to suppress glucose production in the pregnant sheep is greater than that in nonpregnant, fed sheep. These results also demonstrate that differential changes in the effect of insulin can exist simultaneously between peripheral (glucose consuming) and central (glucose producing) tissues. The changes in glucose utilization and in insulin effect in the pregnant sheep are both qualitatively and quantitatively similar to those of the nonpregnant sheep when fasted, suggesting that similar substrate and/or hormonal factors may be involved.     

The effect of glucagon antibodies on plasma glucose and insulin levels

The actions of glucagon and insulin are interrelated as the two hormones have opposite physiological effects and the secretion of insulin is regulated, at least in part, by the level of glucagon. We have found that rabbits which are immunized against glucagon have normal fasting levels of blood glucose but a lowered level of insulin. These rabbits are also able to rapidly utilize intravenously injected glucose butwith a much lower plasma level of insulin. These results demonstrate that in the presence of glucagon antibodies, normal blood sugar levels can be maintained with a reduced supply of insulin. It is suggested that this finding may be useful in the treatment of diabetes.     

Blood glucose and serum insulin levels in lean and genetically obese mice.

Fed and 24 hour fasted lean and genetically obese mice (ob/ob) were given a fixed glucose load per gm body weight by intraperitoneal and intragastric administration. Intraperitoneal glucose injection into the obese mice produced a prolonged elevated blood glucose level with a concomitant significant decrease of circulating insulin. Possible interpretations of this observation are discussed. In those obese animals in which glucose was administered intragastrically the fed obese mice had a blood glucose concentration of 450-500 mg% for a period of one hour but there was no increase in circulating insulin, however, in the fasted obese mice in which the glucose concentration was about 350 mg% for one hour, there was a significant increase in the circulating insulin levels. The fed and fasted lean mice showed normal glucose tolerance curves and the expected increase in circulating insulin following either intraperitoneal orintragastric glucose loads. It is concluded that hyperglycaemia in the ob/ob mice is unlikely to be the principal cause of hyperinsulinaemia.     

Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat

Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat.