Ugo Butturini

Decreased hepatic insulin extraction in subjects with mild glucose intolerance

The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.

Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects

SummaryIn this study, we have measured plasma insulin at fasting and following an oral glucose load and blood pressure after glucose load in 367 (247 non-obese, 120 obese) normotensive and untreated mildly hypertensive subjects. Overall, there was no independent association between fasting plasma insulin levels and blood pressure values. After controlling for age and body weight, a significant relationship between postglucose plasma insulin levels and diastolic blood pressure was found. When non-obese and obese subjects were examined separately, significant relationships were identified between postglucose plasma insulin levels and both systolic and diastolic blood pressure values in the former but not in the latter. A comparison of sex-, age-, and weight-matched hyperinsulinaemic vs normoinsulinaemic subjects showed that the former had significantly higher values of blood pressure only if not obese. These results demonstrate that the plasma insulin response to glucose is independently correlated with blood pressure.

Effect of Age and Environmental Factors on Glucose Tolerance and Insulin Secretion in a Worker Population

The effect of age on glucose tolerance, as differentiated from the effects of obesity, work and leisure physical activity, family history of diabetes, and the use of drugs known to adversely affect glucose tolerance and/or insulin secretion, has been analyzed in 732 factory workers aged 22 to 73 years. Glucose tolerance, as evaluated by the plasma glucose response to 75 g of oral glucose deteriorated with age, associated with an increase in plasma insulin levels. However, the age‐related decrease in glucose tolerance also correlated significantly with degree of obesity, leisure‐time physical activity, and the use of potential diabetogenic drugs. Partial correlation coefficients were calculated to define the effect of age per se on glucose tolerance, controlling for the presence of these other age‐related variables. When this was done, the degree of correlation between age and glucose tolerance was reduced, particularly in women, to where it became of marginal statistical significance. The effect of age on insulin response was affected to a greater degree by age‐related variables, and was no longer statistically significant when these other factors were taken into consideration. These data suggest that the elevation in plasma glucose and insulin levels associated with age are to a certain extent due to age‐related environmental factors, and the deterioration in glucose tolerance with age is relatively modest in magnitude in a generally healthy population.

Influence of the menstrual cycle on glucose tolerance and insulin secretion

To evaluate the impact of the menstrual cycle on glucose tolerance and insulin secretion, in the present study we have measured the plasma concentrations of glucose, insulin, and C-peptide during a 2-hour oral glucose tolerance test in 110 healthy, nonobese, regularly menstruating women. Fifty-five women were in the follicular phase, and 55 were in the luteal phase of the cycle. The two groups were well matched for age and body weight. Plasma concentrations of glucose, insulin, and C-peptide either in the fasting state or after the oral glucose load did not differ in the two groups. These results suggest that in nondiabetic women the menstrual cycle has no major effect on glucose tolerance and insulin secretion and that the phase of the menstrual cycle should not be considered in programming and interpreting an oral glucose tolerance test.

Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in non-diabetic subjects

A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects. Metformin (1 g) was administered as a bolus in a peripheral vein and blood was sampled 2, 5, 10, 15 and 30 minutes after the drug injection. No significant change in fasting concentration of glucose nor in C-peptide, insulin, glucagon and growth hormone fasting levels was noticed. It is concluded that metformin does not possess an acute direct hypoglycaemic effect in non-diabetic subjects and does not acutely affect the basal activity of endocrine pancreas and pituitary gland in releasing insulin, glucagon and growth hormone.

Combined sulphonylurea-biguanide therapy for non-insulin dependent diabetics. Metabolic effects of glibenclamide and metformin or phenformin in newly diagnosed obese patients

SummaryFasting, pre-prandial and post-prandial blood glucose levels and blood lactate, blood pyruvate, serum cholesterol, serum triglycerides and body weight were measured in 30 obese, newly diagnosed, non-insulin-dependent diabetics at the end of 4 subsequent periods of different regimens, each lasting for 5 days. In the first period, patients remained on free diet; in the second period, a hypocaloric diet (20 kcal/kg IBW) was followed; in the third period, glibenclamide (2.5 mg 3-times daily) was added to hypocaloric diet. During the last period, the patients were divided into two groups: Group A (15 patients) received, in addition to diet and glibenclamide, phenformin (25 mg 3-times daily) and Group B (15 patients) received, in addition to diet and glibenclamide, metformin (500 mg 3-times daily). Five similar patients served as controls and, at the end of the free-diet period, were put on hypocaloric diet and continued this regimen throughout the study period. The results showed that biguanides allowed...

Nicotinic-cholinergic involvement in arginine-vasopressin response to insulin-induced hypoglycemia in normal men

In order to establish whether arginine-vasopressin (AVP) release in response to insulin-induced hypoglycemia is mediated by a muscarinic and/or nicotinic cholinergic pathway, 12 normal men had an insulin tolerance test (ITT) in basal conditions and after treatment with the muscarinic receptor blocker pirenzepine (40 mg IV (intravenously) ten minutes before ITT in six subjects) or the nicotinic receptor antagonist trimethaphan (0.3 mg/min X 30 min IV before ITT in six subjects). The drugs did not modify arterial blood pressure nor produce side effects capable of altering AVP secretion. Pirenzepine administration did not change AVP response to hypoglycemia, whereas trimethaphan significantly reduced AVP increase by about 50% during the ITT. These data suggest the involvement of a cholinergic-nicotinic mechanism in regulation of AVP response to hypoglycemia.

Muscarinic cholinergic modulation of insulin response to an intravenous glucose tolerance test in normal man

The effect of pirenzepine, a specific muscarinic cholinergic receptor antagonist, on insulin and glucagon responses to an intravenous injection of glucose was investigated in eight normal adult subjects. These volunteers received two iv glucose tolerance tests (0.33 g/kg) before and after the oral administration of 125 mg of pirenzepine (three doses of 25 mg during the day before the experiment and a fourth dose of 50 mg 2 h before glucose injection). Treatment with pirenzepine neither altered basal blood glucose levels nor affected glucose tolerance after the injection of the glucose load. In addition, it did not modify basal plasma insulin and glucagon levels and the decrement of glucagon in response to glucose injection. In contrast, pirenzepine significantly decreased insulin release induced by glucose administration. In man, during the present experimental conditions, the muscarinic cholinergic system modulates insulin, but not glucagon response to an iv glucose injection.

Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases

SummaryIn the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.

TSH and PRL Responses to Domperidone and TRH in Men with Insulin-Dependent Diabetes Mellitus of Different Duration

The effect of domperidone, a specific blocker of dopamine receptors, on serum TSH and PRL levels was evaluated in 16 euthyroid men affected by insulin-dependent diabetes mellitus (IDDM) of different duration and in 7 age-matched normal controls. Diabetics were divided into 2 groups of 8 men according to the duration of their disease (group I: 1-9 years; group II: 11-18 years). Both groups had normal basal levels of TSH and PRL. Responses of these hormones to domperidone were similar in normal controls and in group I diabetics, whereas they were significantly reduced in patients of group II. When all 16 diabetics were studied together, a significant negative correlation was found between mean maximal peaks of TSH and PRL responses to domperidone and duration of diabetes. In order to evaluate whether the reduced effect of domperidone in diabetics was due to alterations of the dopaminergic control of TSH and PRL secretion, the domperidone test was repeated in 6 normal controls and in 6 diabetics of group II after infusion of dopamine (4 micrograms/kg/min for 2 h). Dopamine infusion induced parallel decreases in TSH and PRL concentrations, without modifying hormonal secretory patterns in response to domperidone. These data suggested that the reduced TSH and PRL responses to domperidone in diabetics were not due to alterations of the dopaminergic control of pituitary function but to a defect at the pituitary level. To test this hypothesis, TSH and PRL responses to TRH were evaluated in group I and group II diabetics and in normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)