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Biomedical subjects

M Muggeo

Publications and source records attributed to M Muggeo.

At least 19 recordsLinked to original sources
PubMed1992

Studies on the mechanism of action of sulphonylureas in type II diabetic subjects: gliquidone.

The mechanism of action of sulphonylureas is not completely understood. In the present study we evaluated the effects of gliquidone, a second-generation compound, on several metabolic parameters in 22 patients with untreated newly-diagnosed type II (noninsulin-dependent) diabetes mellitus. After either 1 or 6 months of treatment with gliquidone plus isocaloric diet we observed: 1) a significant decrease in fasting plasma glucose and glycemic profile after oral glucose load; 2) unchanged fasting and postglucose plasma insulin levels; 3) no change in fasting C-peptide levels but a significant increase in C-peptide concentrations after glucose challenge; 4) a significant increase in glucose disappearance rate from plasma following iv insulin injection; 5) an increase in the insulin-induced reduction of plasma levels of free-fatty acids; 6) no change in plasma C-peptide levels following iv insulin injection; 7) a significant increase in specific insulin binding to monocytes. After 6 but not 1 month of gliquidone therapy we also found an increase in the activity of hexokinase in circulating mononuclear leukocytes. These results suggest that the hypoglycemic effect of gliquidone occurs through either an increased beta cell response to glucose stimulus or an enhanced insulin sensitivity. The latter effect seems to depend on both receptor and postreceptor mechanisms.

Administration, Oral↗
PubMed1992

Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis.

Denaturing gradient gel electrophoresis (DGGE) has been used to screen for mutations in the insulin receptor gene. Each of the 22 exons was amplified by the polymerase chain reaction (PCR). For each exon, one of the two PCR primers contained a guanine-cytosine (GC) clamp at its 5' end. The DNA was analyzed by electrophoresis through a polyacrylamide gel containing a gradient of denaturants. Two geometries for the gels were compared; the gradient of denaturants was oriented either parallel or perpendicular to the electric field. The sensitivity of the technique was evaluated by determining whether DGGE succeeded in detecting known mutations and polymorphisms in the insulin receptor gene. With parallel gels, 12 of 16 sequence variants were detected. The use of perpendicular gels increased the sensitivity of detection so that all 16 sequence variants were successfully detected when DNA was analyzed by a combination of perpendicular and parallel gels. Furthermore, DGGE was used to investigate a patient with leprechaunism whose insulin receptor genes had not previously been studied. Two mutant alleles were identified in this patient. The allele inherited from the father had a mutation substituting alanine for Val-28; in the allele inherited from the mother, arginine was substituted for Gly-366.

Alanine↗
PubMed1990

Glucose and insulin suppression of plasma free fatty acids in obese subjects with normal glucose tolerance or mild, newly diagnosed type 2 (non-insulin-dependent) diabetes.

The in vivo suppressive effect of glucose and insulin on plasma free fatty acid concentrations was investigated in obese subjects with (n = 6) and without (n = 6) Type 2 (non-insulin-dependent) diabetes mellitus during a 4h-hyperglycemic glucose clamp (about 11.2 mmol/l). Somatostatin was infused (250 micrograms/h) during the third h of glucose clamp to inhibit glucose-stimulated insulin secretion. Plasma insulin values were similar in the two groups at fasting and all throughout the study (F = 0.04; p = NS, two way analysis of variance), while the amount of glucose metabolized during the clamp was lower in diabetic subjects. Plasma free fatty acid concentrations, which were similar in the two groups at fasting, decreased during hyperglycemia and glucose-induced hyperinsulinemia (0-120 min; 180-240 min), and rose during hyperglycemia and somatostatin-inhibited insulin secretion (120-180 min). However, plasma free fatty acid concentrations were significantly higher in diabetic subjects all along the study period both in absolute terms (F = 11.4; p less than 0.0001) and when individual data were recalculated as percent of fasting value (F = 13.3; p less than 0.0001). Our data suggest that suppressibility of fasting plasma free fatty acids is lower in obese Type 2 diabetes in comparison with obese non-diabetic subjects.

Adult↗
PubMed1990

Normal inhibition by somatostatin of glucose-stimulated B cell secretion in the obese subjects.

Aim of the present study was to evaluate whether the inhibitory effect of somatostatin on pancreatic B-cell secretion is normal in nondiabetic obese subjects. For this purpose plasma C-peptide concentrations were measured in 10 nondiabetic obese subjects and 10 nonobese healthy controls during a 4-h hyperglycemic (11 mmol/l) glucose clamp. Somatostatin was infused (2.5 nmol/min) during the third hour of the study period in order to inhibit glucose-stimulated B-cell secretion. Fasting C-peptide averaged 0.46 +/- 0.04 nmol/l (mean +/- SEM) in nonobese subjects, and 0.85 +/- 0.08 nmol/l in obese patients (P less than 0.001). In the period 0-120 min the area under the plasma C-peptide curve was significantly higher in obese than in nonobese subjects (292 +/- 23 vs. 230 +/- 17 nmol/l x 120 min, P less than 0.05), however, in the last 20 min of the glucose infusion period without somatostatin (100-120 min) plasma C-peptide was not significantly different in the two groups (2.94 +/- 0.32 nmol/l in nonobese subjects and 3.21 +/- 0.19 nmol/l in obese patients, p = NS). During somatostatin infusion while maintaining hyperglycemia, plasma C-peptide decreased in both groups, and in the period 160-180 min it averaged 0.89 +/- 0.12 nmol/l in control subjects and 0.93 +/- 0.08 nmol/l in obese patients (P = NS), with a percent reduction similar in the two groups (70 +/- 2% in controls and 71 +/- 2% in obese patients). After discontinuing somatostatin infusion, plasma C-peptide increased to concentrations which were higher in obese than in nonobese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Enzymatic activities related to intermediary metabolism of glucose in circulating mononuclear cells from obese humans: relationship to enzyme activity in adipose tissue.

In order to assess whether enzyme activities of glucose metabolism measured in mononuclear blood cells reflect those in a typical insulin target tissue, we studied hexokinase, 6-phosphofructokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities in lymphomonocytes and in hypogastric adipose tissue from 15 nondiabetic obese women. Statistically significant relationships were found in the activities of hexokinase (r = 0.53, p less than 0.05), 6-phosphofructokinase (r = 0.85, p less than 0.01), and 6-phosphogluconate dehydrogenase (r = 0.72, p less than 0.01) between the two tissues. These results suggest that mononuclear blood cells may be suitable as a model for studying cytosolic key enzymes involved in the glucose metabolism of humans.

Adipose Tissue↗
PubMed1990

Plasma concentrations of growth hormone during hyperglycemic clamp with or without somatostatin infusion in obese subjects.

It is known that obese subjects have a blunted GH secretory response to stimulation, but little is known about the inhibition of GH secretion in obesity. The present study was designed to evaluate the effects of obesity on the suppression of GH by hyperglycemia and/or somatostatin. Plasma GH concentrations were measured in eight nondiabetic obese subjects and eight nonobese healthy controls during a 4-h hyperglycemic clamp. During the third hour synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min. Baseline plasma GH levels were similar in obese and nonobese subjects (0.9 +/- 0.1 vs. 0.8 +/- 0.2 micrograms/L; mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma GH averaged 0.8 +/- 0.1 micrograms/L in obese patients and 0.4 +/- 0.1 micrograms/L in control subjects (P less than 0.01), with a reduction of 6 +/- 5% in the former and 35 +/- 10% in the latter (P less than 0.01). In both groups somatostatin infusion did not result in a further decrease in plasma GH. Discontinuation of the somatostatin infusion resulted in a rise in both groups; the increase was higher in nonobese subjects (8.1 +/- 3.8 vs. 2.3 +/- 0.9 micrograms/L in the period 220-240 min; P = NS). These results suggest that in human obesity, hyperglycemia has a diminished inhibitory effect on GH secretion, and somatostatin administration has no additional effect in either obese or nonobese nondiabetic subjects.

Analysis of Variance↗
PubMed1990

Plasma free fatty acid concentration during hyperglycemic glucose clamp with and without somatostatin infusion in obese subjects with normal glucose tolerance.

In the present study we evaluated the regulation of plasma free fatty acid (FFA) concentration by glucose and insulin in human obesity. To this purpose we measured plasma FFA concentration in normoglycemic, normoinsulinemic obese (n = 8) and nonobese (n = 8) healthy subjects during 240 min of exogenous hyperglycemia (hyperglycemic glucose clamp) in presence of both glucose-stimulated (0-120 min and 180-240 min) and somatostatin-inhibited (120-180 min) insulin secretion. We found that plasma FFA curves were roughly parallel in the 0-120 min period and FFA values of obese subjects were constantly higher throughout the experimental period. Moreover, the difference between the two groups was significant when individual data were expressed as a percent of fasting FFA value (P less than 0.0001 from 0 to 120 min). Plasma insulin levels were similar in the two groups during the entire study. The amount of glucose metabolized during the 80-120 min period was significantly lower in obese than in nonobese subjects (172 +/- 7 v. 341 +/- 11 mg/m2.min, P less than 0.01; means +/- s.e.). During the somatostatin period (120-180 min) plasma insulin was lowered close to basal values in both groups (116 +/- 15 and 109 +/- 11 pmol/l) and plasma FFA concentrations rose in a linear fashion. Our data suggest that suppression of plasma FFA concentrations by glucose and insulin is qualitatively similar in healthy nonobese and obese subjects, the latter having higher FFA values. Insulin action on FFA metabolism isn ot grossly impaired in obese subjects who are clearly insulin resistant as far as glucose metabolism is concerned.

Adult↗
PubMed1990

[Hypoglycemia].

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Adult↗
PubMed1990

B cell secretion and insulin sensitivity in hypertensive and normotensive obese subjects.

To test the hypothesis that in obesity hypertension is associated with more pronounced hyperinsulinaemia and insulin resistance we compared plasma insulin levels and insulin sensitivity in a group of 6 obese subjects with untreated hypertension and in a group of 6 obese subjects with normal blood pressure. The two groups were similar for sex, age, body mass index and glucose tolerance. Six nonobese subjects served as controls. The study consisted of a 2-h hyperglycaemic clamp (steady-state plasma glucose = 11 mmol/l) and a 15-min insulin tolerance test (0.1 U/kg body wt). During hyperglycaemic clamp, insulin and C-peptide plasma levels were similar in normotensive and hypertensive obese subjects: the area under the plasma insulin curve was 36,000 +/- 3000 pmol/l X 120 min in the former and 34,000 +/- 1000 pmol/l X 120 min in the latter; the area under the plasma C-peptide curve was 298,000 +/- 26,000 pmol/l X 120 min in the former and 246,000 +/- 26,000 pmol/l X 120 min in the latter (P = n.s.). The ratio M/I between the amount of glucose metabolized (M) and the mean plasma insulin levels (I) during hyperglycaemic clamp was similar in the two groups: 0.59 +/- 0.09 in normotensive and 0.58 +/- 0.08 mg/min X m2 per pmol/l in hypertensive obese subjects (P = n.s.). Also the rate coefficient of glucose disappearance from plasma (K(itt)) after i.v. insulin injection was similar in the two groups (4.08 +/- 0.51 vs. 3.87 +/- 0.53 per cent/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies.

We compared estimates of in vivo insulin action derived from insulin tolerance tests (ITT) and euglycemic and hyperglycemic glucose clamp studies in 17 normal subjects and 19 patients with various diseases characterized by insulin resistance. Fifteen subjects underwent an ITT and a euglycemic clamp study, 17 subjects underwent an ITT and a hyperglycemic clamp study, and 4 subjects underwent all 3 tests. The ITT consisted of a bolus iv injection of regular insulin (0.1 U/kg BW). The plasma glucose disappearance rate during the 3- to 15-min period following the insulin injection was taken as a measure of insulin action. In both euglycemic and hyperglycemic clamp studies, which were carried out with standard techniques, the ratio between the amount of glucose infused to maintain glycemia at the desired level and the mean plasma insulin concentration from 60-120 min (M) (euglycemic clamp studies) or 20-120 min (I) (hyperglycemic clamp studies) was used as a measure of insulin action. A close correlation was found between plasma glucose disappearance rate and the M/I ratio during either the euglycemic (r = 0.811; P less than 0.001) or the hyperglycemic (r = 0.826; P less than 0.001) clamp studies. These results suggest that the 15-min ITT is suitable as a simple and rapid estimation of in vivo insulin action when glucose clamp studies are not feasible, as in large series of subjects or serial studies.

Adult↗
PubMed1988

Differences in glucose metabolic enzyme activities in human adipose tissue from abdominal and gluteal regions.

In order to verify whether intersite differences exist in glucose metabolism of subcutaneous human adipose tissue, basal and insulin-stimulated 14C-1-glucose incorporation into triglycerides and the activities of some enzymes of glucose disposal were tested in abdominal and gluteal adipose tissue of 31 nondiabetic obese otherwise healthy women during isocaloric diet and after 2 weeks of very-low-calorie-protein-sparing modified diet. Basal 14C-1-glucose incorporation into triglycerides was quite similar in the adipose tissue of the two sites, and it was not influenced by dietary restriction. Insulin stimulated this metabolic activity to the same extent in both sites during isocaloric diet; after hypocaloric diet this effect of insulin was slightly decreased in adipose tissue of the abdominal site and completely abolished in the gluteal site. No enzymatic activity was different between the examined subcutaneous regions during the isocaloric diet; after very-low-calorie intake, hexokinase activity decreased in both sites, once again more markedly in the gluteal one; glucose-6-P-dehydrogenase activity decreased in the adipose tissue of the gluteal region only. These data suggest that glucose metabolism of the adipose tissue of the gluteal region is particularly decreased by severe calorie restriction. Therefore, since lipolysis does not occur at a higher rate in gluteal adipose tissue during calorie restriction, this tissue seems to undergo a resting metabolic phase during hypocaloric diet.

Abdomen↗
PubMed1987

Insulin receptors on circulating blood cells from patients with pancreatogenic diabetes: a comparison with type I diabetes and normal subjects.

We studied 125I-insulin binding to erythrocytes from 14 patients with diabetes secondary to chronic pancreatitis or pancreatectomy and compared the results with those found in 10 patients with type I diabetes and 25 normal controls. Patients with pancreatogenic diabetes had higher 125I-insulin binding and enhanced tissue sensitivity to exogenous insulin measured with the glucose clamp technique as compared with patients with type I diabetes. Similar binding data were obtained with monocytes from 3 patients with pancreatogenic diabetes. The increase in insulin binding seemed due mainly to an increase in receptor number. The increase in insulin binding to cells from patients with pancreatogenic diabetes in comparison with cells from normal subjects was also seen in young-erythrocyte-rich fractions and in old-erythrocyte-rich fractions obtained from the mixed population of circulating erythrocytes by centrifugation in density gradient of Percoll-Pielografin. These data, in the absence of any sign of major hematological disorders, suggest that the increase in insulin receptors seen in erythrocytes and in monocytes from patients with pancreatogenic diabetes, can mirror a general phenomenon on tissues throughout the body, including major target cells for insulin and correlate with the heightened sensitivity to insulin characteristic of these patients. In conclusion, patients with pancreatogenic diabetes have increased insulin binding as compared to controls and to patients with type I diabetes with chronic hypoinsulinemia of the same degree. Thus, in addition to insulin deficiency, other factor (s), such as glucagon deficiency, are responsible for the clinical and metabolic differences between these two conditions of insulin deficiency.

Blood Cells↗
PubMed1985

High serum levels of angiotensin-converting enzyme in untreated Addison's disease.

Serum angiotensin-converting enzyme (ACE) in four patients with untreated Addison's disease was significantly higher [79.7 +/- 17.5 (SD) nmol min-1 ml-1] than in normal subjects (37.7 +/- 8.9 nmol min-1 ml-1, P less than 0.02). During corticosteroid hormone replacement therapy the enzyme levels returned within the normal range (44.0 +/- 7.6 nmol min-1 ml-1). In two additional patients the enzyme was assayed only while they were receiving therapy and found normal (38 and 52 nmol min-1 ml-1, respectively). In one of them, an increase ACE level (70 nmol min-1 ml-1) was found after therapy was reduced by 50%. Primary adrenal insufficiency is another disease in which ACE levels may be increased.

Addison Disease↗