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Biomedical subjects

D Giugliano

Publications and source records attributed to D Giugliano.

At least 163 records · Page 9Linked to original sources
PubMed1987

Daily rapid blood glucose variations may condition antithrombin III biologic activity but not its plasma concentration in insulin-dependent diabetes. A possible role for labile non-enzymatic glycation.

The effect of rapid daily variation of glycemia and labile HbA1 on both antithrombin III (ATIII) activity and plasma concentration in ten insulin dependent diabetics has been evaluated. The variations of both plasma glucose and labile HbA1 were inversely correlated to the alterations of ATIII activity (r = -0.71 and r = -0.73, respectively, p less than 0.001), while no change in ATIII plasma concentration was present. These data suggest a direct role of glucose in determining rapid alteration of ATIII biologic activity, in vivo, in diabetes, probably mediated by labile non-enzymatic glycation.

Adult↗
PubMed1986

Insulin induces opposite changes in plasma and erythrocyte magnesium concentrations in normal man.

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrophotometry in 10 healthy volunteers during an oral glucose tolerance test and during an euglycaemic hyperinsulinaemic glucose clamp. At min 180 and 210 of the oral glucose tolerance test, a significant decline in plasma magnesium levels (p less than 0.01 and p less than 0.05 respectively) and a significant increase in erythrocyte magnesium levels (p less than 0.01 and p less than 0.05 respectively) were observed. Similar changes were seen during the second hour of the glucose clamp, during which euglycaemia (4.1 +/- 0.4 mmol/l) was maintained despite hyperinsulinaemia (110-130 mU/l). During in vitro incubations, glucose (5 mmol/l) did not modify erythrocyte magnesium levels. In contrast, erythrocyte magnesium levels were significantly increased (p less than 0.01) by insulin (100 mU/l), an effect entirely abolished by ouabain (5 X 10(-4) mol/l). These results suggest that insulin induces a shift of magnesium from the plasma to the erythrocytes both in vivo and in vitro. These data may help to interprete the abnormalities in magnesium circulating levels frequently reported in diabetic patients.

Adult↗
PubMed1986

Impaired insulin response to glucose but not to arginine in heroin addicts.

Plasma glucose, insulin, glucagon and growth hormone responses to both oral glucose and iv arginine were evaluated in 15 heroin addicts and 15 control subjects matched for age, sex and weight. The heroin users had an exaggerated rise in plasma glucose concentrations following oral sugar, which persisted until the end of the study (102 +/- 5 mg/dl in addicts vs 72 +/- 3 mg/dl in controls at 240 min, p less than 0.01) and significantly lower insulin responses (insulin peak 28 +/- 4 microU/ml in addicts vs 67 +/- 8 microU/ml in controls, p less than 0.01). The inhibitory effect of glucose on glucagon concentrations was less evident in addicts than in controls. The responses of plasma glucose, insulin and glucagon to arginine were not significantly different between addicts and controls, while the growth hormone rise was significantly greater in addicts. These results demonstrate that heroin users have impaired insulin secretion to oral glucose but not to arginine and suggest that: the impaired insulin secretion in heroin addicts is not dependent on beta-cell exhaustion, and a selective inhibition of glucose-induced insulin secretion is operative in these subjects, as it happens in patients with noninsulin-dependent diabetes mellitus.

Adult↗
PubMed1986

Heparin preserves antithrombin III biological activity from hyperglycemia-induced alterations in insulin-dependent diabetics.

Alteration in antithrombin III (ATIII) biological activity, despite its normal plasma concentration, in diabetic subjects is shown in this report. This alteration is glycemia level-dependent, there existing an inverse correlation between fluctuations of daily blood glucose level, labile glycosylated hemoglobin and ATIII activity. The subcutaneous and endovenous heparin administration restores ATIII activity, but does not modify its plasma concentration in diabetics. Moreover, heparin treatment preserves ATIII activity from glycemia-induced alterations. These data suggest a role for glucose, probably through a labile nonenzymatic glycation process, in determining the alteration of ATIII biological activity. Moreover, showing the possibility by heparin administration to restore ATIII activity and preserve its biological function from effects of glycemia variations, stress the hypothesis that glucose and heparin compete in vivo, both against the same catalytic residue of ATIII.

Adult↗
PubMed1986

Combined insulin and sulfonylurea therapy in non-insulin-dependent diabetics with secondary failure to oral drugs: a one year follow-up.

We studied the influence of chronic sulfonylurea treatment on glucose metabolism and beta-cell secretory activity in diabetic patients requiring insulin after secondary failure to oral drugs. Thirty diabetics were allocated at random into two groups, each consisting of 15 subjects: group A continued insulin treatment, while group B received combined insulin plus sulfonylurea. Daily doses of the sulfonylurea gliclazide ranged from 40 to 240 mg, and dose adjustment was made on the basis of periodic monthly control. This treatment (12 months) caused a significant improvement of both diurnal glucose profile and HbA1 levels; the beta-cell secretory response to 1 mg glucagon was significantly increased at the end of the study. There was on average a 40% reduction of the daily insulin dose in the diabetics receiving combined treatment. None of these improvements were seen in the control group receiving only insulin for the same period of time. We suggest that combining a sulfonylurea with insulin can be useful in insulin-requiring type-2 diabetics who still secrete some endogenous insulin.

Adult↗
PubMed1985

Effects of salicylate, tolbutamide, and prostaglandin E2 on insulin responses to glucose in noninsulin-dependent diabetes mellitus.

To assess whether the beneficial effects of salicylates compounds and sulfonylureas on insulin secretion in patients with noninsulin-dependent diabetes mellitus could be ascribed to inhibition of prostaglandin E (PGE) synthesis, insulin responses to iv glucose pulses were determined in diabetic patients during infusion of lysine acetylsalicylate (LAS) or tolbutamide, with or without a concurrent infusion of PGE2. In these diabetic patients, the augmenting effects of LAS on glucose-induced insulin secretion were abolished by PGE2 infusion. Partial restoration by tolbutamide infusion of the first and second phases of glucose-induced insulin secretion was not affected by the administration of PGE2. The stimulatory effects of LAS and tolbutamide on insulin secretion were additive, suggesting separate mechanisms of action. Since salicylates and sulfonylureas lower plasma glucose concentrations, we also evaluated whether prevention of the fall in the prestimulus glucose level could result in a further amplification of insulin release. Resetting the prestimulus glucose level to control values by infusing glucose caused a further increase in the second, but not the first, phase of glucose-induced insulin secretion, indicating that the prestimulus glucose level had a role in regulating subsequent insulin release. These results indicate that salicylates, but not sulfonylureas, exert their acute insulinotropic effect in noninsulin-dependent diabetic patients by inhibiting endogenous PGE synthesis and support the idea that endogenous PGE may play a role in the impaired insulin response to glucose in this form of human diabetes.

Adult↗
PubMed1985

Normalization by sodium salicylate of the impaired counterregulatory glucagon response to hypoglycemia in insulin-dependent diabetes. A possible role for endogenous prostaglandins.

The present study was undertaken to evaluate the influence of sodium salicylate on the counterregulatory glucagon response to insulin-induced hypoglycemia in both insulin-dependent diabetic subjects (IDDM) and normal controls. The IDDM group consisted of 5 patients with recent onset of disease (less than 45 days), a normal glucagon response to hypoglycemia, and no detectable insulin antibodies (group 1); and 7 patients with duration of disease between 1 and 5 yr, a reduced glucagon response to hypoglycemia, and no insulin antibodies (group 2). Ten healthy subjects served as a control group. The infusion of sodium salicylate (40 mg/min) during insulin-induced hypoglycemia (1 mU/kg-min for 60 min) in normal subjects caused a significant increase of the counterregulatory glucagon response both in terms of glucagon peak and integrated areas. Sodium salicylate itself significantly increased basal insulin and decreased glucose, but did not change basal glucagon. In the diabetic subjects of group 1, sodium salicylate amplified the glucagon response to the same degree of hypoglycemia without affecting the rates of glucose fall and recovery. Compared with normals and diabetic subjects of group 1, diabetic subjects of group 2 presented, in basal conditions, a reduced glucagon response to hypoglycemia and a slower rate of glucose recovery. Sodium salicylate normalized both defects. These results indicate that sodium salicylate may augment glucagon responses by improving the recognition of hypoglycemia in both normals and IDDM. Moreover, the restoration by sodium salicylate of a normal glucagon response to hypoglycemia in diabetic subjects of group 2 suggests a role for endogenous prostaglandins in this selective deficiency of the counterregulatory response.

Adolescent↗
PubMed1985

Interaction between epinephrine, prostaglandin E, and met-enkephalin in the regulation of insulin release in man.

Prostaglandin E (PGE), epinephrine and metenkephalin are three endogenous substances normally present in the endocrine pancreas which have been reported to inhibit glucose-induced insulin secretion in normal humans. To evaluate possible synergistic interactions between these inhibitory agents upon the regulation of insulin release in man, we examined the effects of PGE, epinephrine and the long-acting met-enkephalin analogue FK 33-824, given alone or in combination, upon glucose-induced insulin secretion in normal man. The infusion of the three agents at doses known to affect insulin secretion (10 micrograms/min, 15 ng/kg/min, 0.5 mg im, respectively) produced the expected inhibitory effects upon insulin responses to an intravenous glucose challenge. The infusion of the three agents at doses which did not produce per se any significant change of insulin responses to glucose (5 micrograms/min, 5 ng/kg/min, 0.2 mg i.m., respectively), caused a significant inhibition of this response when given in combination. In particular, the acute insulin response to glucose decreased from a control value of 50 +/- 9 microU/ml to a value of 21 +/- 6 microU/ml (p less than 0.02). The inhibitory effect of epinephrine (15 ng/kg/min) upon glucose-induced insulin secretion was partially reversed by sodium salicylate, an inhibitor of endogenous prostaglandin synthesis, which increased but not normalized, either the acute insulin response and the glucose disappearance rates. Similarly, the negative effect of FK 33-824 upon glucose-induced insulin secretion was reversed by sodium salicylate. Similar findings were also obtained with indomethacin, another structurally unrelated inhibitor of endogenous prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Impaired insulin secretion in human diabetes mellitus. Interactions between naloxone, phentolamine and lysine acetylsalicylate upon glucose induced insulin release.

Non insulin-dependent diabetes mellitus (Type II) is characterized by the loss of the acute insulin response to glucose. Met-enkephalin, catecholamines and prostaglandin E (PGE) have all been reported to inhibit the acute insulin response to glucose in normal humans. To evaluate the hypothesis that an increased sensitivity to these endogenous substances may play a role in defective insulin secretion in diabetes, we evaluated the effects of three blocking drugs upon the impaired insulin response to glucose in Type II diabetic subjects, as well as glucose-induced insulin secretion in normal humans. In diabetics, acute insulin responses to glucose were significantly increased by all the agents tested (naloxone, phentolamine and lysine acetylsalicylate), but only the cyclooxygenase inhibitor significantly augmented second phase insulin secretion and glucose disappearance rates. The combined infusion of the three agents caused a striking increase of the acute insulin response to glucose (response before: 3 +/- 2 uU/ml; after: 22 +/- 6 uU/ml, p less than 0.01). This was accompanied by a ninefold augmentation of the second phase of insulin secretion which was the result of a synergistic interaction between the three drugs (response significantly higher than the sum of single effects). In normals, insulin responses to glucose were also significantly increased by the combined infusions of the drugs, but to a significantly lesser extent than that of diabetics. This different degree of insulin potentiation between normals and diabetics under the infusion of the three agents persisted even when the prestimulus glucose level of normals was matched to that of diabetics by a glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗