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Biomedical subjects

A Quatraro

Publications and source records attributed to A Quatraro.

At least 55 records · Page 3Linked to original sources
PubMed1987

Induced hyperglycemia alters antithrombin III activity but not its plasma concentration in healthy normal subjects.

The effects of induced hyperglycemia on both antithrombin III (ATIII) biologic activity and plasma concentration in normal subjects are reported. A decrease in ATIII activity parallel to hyperglycemia was observed, while ATIII concentration was unchanged. When the glycemia returned to basal values ATIII activity concomitantly showed values in the basal range. Heparin infusion was able to significantly preserve ATIII activity from glycemia-induced alterations. These data demonstrate that hyperglycemia by itself may alter ATIII biologic activity. Moreover, the effect of heparin administration suggests that both glucose and heparin compete in vivo for the same functional site. Our study, showing the possible role of hyperglycemia in altering the biologic function of some proteins, stresses the role of increased blood glucose in the development of some complications in diabetes.

Adult↗
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

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

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↗
PubMed1983

Glucose tolerance and hormonal responses in heroin addicts. A possible role for endogenous opiates in the pathogenesis of non-insulin-dependent diabetes.

Plasma glucose, insulin, glucagon, and growth hormone responses to intravenous glucose stimulation were investigated in 15 heroin-dependent men and in 15 control subjects matched for age, sex, and weight. Although the fasting concentrations of insulin, glucagon, and GH were significantly higher in the heroin addicts, they had markedly reduced plasma insulin responses to intravenous glucose (acute insulin response, calculated as the mean change in insulin levels over 3 to 10 minutes: 10 +/- 5 microU/mL in the addicts v 44 +/- 9 microU/mL in the controls, P less than 0.001) and glucose utilization rates in the diabetic range (KG: 0.96 +/- 0.09%/min in the addicts v 1.65 +/- 0.10%/min in the controls, P less than 0.01). These results show that chronic heroin administration produces a state of fasting hyperinsulinemia even in the absence of obesity, glucose intolerance, and a marked reduction of the first phase of insulin secretion. A possible role for endogenous opiates in the pathogenesis of non-insulin-dependent diabetes is hypothesized.

Adolescent↗
PubMedDate not supplied

Impaired insulin secretion in human diabetes mellitus. Effect of pharmacological activation of gamma-aminobutyric acid system.

To evaluate whether the gamma-aminobutyric acid (GABA)ergic system plays a role in the defective insulin secretion in human diabetes mellitus, 15 non-insulin-dependent diabetics with fasting hyperglycemia above 140 mg/dl were submitted to two consecutive i.v. glucose tolerance tests (IVGTT) (0.33 g/kg b.w.), in basal conditions and after pharmacologic activation of the GABA system with baclofen and sodium valproate. Baclofen, a synthetic analogue, was given to 8 diabetics in two divided doses of 10 mg each 8h and 1h before the post-treatment test; sodium valproate, a drug that increases endogenous GABA activity, was given orally (800 mg) 60 min before the performance of the post-treatment IVGTT. Neither treatment brought about significant changes in insulin, C-peptide, glucagon or growth hormone responses to i.v. glucose nor did they significantly change glucose disappearance rates. These results seem to indicate that GABA does not play a major role in the pathogenesis of defective insulin secretion in non-insulin-dependent diabetes mellitus.

Aged↗
PubMedDate not supplied

Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

Adult↗
PubMedDate not supplied

Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts.

Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p less than 0.01 vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5 +/- 4 microU/ml to 88 +/- 11 microU/ml, p less than 0.001) and restored to normal the reduced glucose tolerance (KG from 1.10 +/- 0.1% min-1 to 2.04 +/- 0.19% min-1). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.

Adolescent↗
PubMedDate not supplied

The combined insulin and sulfonylurea therapy in diabetes of elderly people.

The usefulness and safety of the combined insulin-sulfonylurea (gliclazide) therapy were investigated in 70 elderly diabetic patients poorly controlled by insulin alone. More than half (45 diabetics, 64% of total) ameliorated significantly their metabolic control after six months of the combined treatment: not only the glycemic profile and glycated hemoglobin Alc were significantly decreased, but the daily insulin dose was reduced by approx. 35% (p < 0.01). These positive results in terms of improved glycemic control as well as reduction of daily insulin needs were still present after a mean period of follow-up of 5 years. The good percentage of positive results, the small incidence of hypoglycemic episodes and the consistent reduction of peripheral hyperinsulinism make this intervention (insulin-gliclazide) a safe strategy that can be adopted in a population of elderly diabetics, poorly controlled on insulin alone.

Journal Article↗
PubMedDate not supplied

Hyperglycemia counterbalances the antihypertensive effect of glutathione in diabetic patients: evidence linking hypertension and glycemia through the oxidative stress in diabetes mellitus.

Diabetes mellitus is associated with hypertension. An antihypertensive effect of the antioxidant glutathione has been recently demonstrated. It has been suggested that hyperglycemia may contribute to the pathophysiology of hypertension in diabetes by generating an oxidative stress. In this study, three different tests were performed in ten hypertensive and ten nonhypertensive diabetic subjects: (1) an oral glucose tolerance test, (2) glutathione i.v. administration (1 g/m2 bolus + 1 g/m2 in 2 h), and (3) oral glucose tolerance test + glutathione administration. At -15', 0', 30', 60', 90', 120', and 180' systolic and diastolic blood pressure, plasma glucose, and insulin were measured. Variations in plasma glucose and insulin levels were not different during each test in the two groups of patients and in test (1) compared to (3). Glutathione administration reduced systolic and diastolic blood pressure in both hypertensive and nonhypertensive diabetic subjects from 30' to 120'. This phenomenon was abolished as glycemia increased after oral glucose loading. In hypertensive, but not in nonhypertensive diabetic subjects, a significant increase of systolic and diastolic blood pressure was observed at 90' and 120' of the oral glucose tolerance test (p < 0.01). These data show that hyperglycemia can counteract the hypotensive effects of the antioxidant glutathione, suggesting that glucose may impair arterial relaxation by producing free radicals. Also, it appears that hypertension in diabetic patients is aggravated by high glucose plasma levels.

Antihypertensive Agents↗
PubMedDate not supplied

Restoration of sensitivity to sulfonylurea after strict glycaemic control with insulin in non-obese type 2 diabetic subjects.

Ten non-obese type 2 diabetic patients with secondary failure to sulfonylureas received an intensive insulin therapy (four doses schedule) for 90 days. The glycaemic control was poor at entry (HbA1c = 11.7 +/- 1.2%) and ameliorated significantly after insulin (HbA1c = 7.1 +/- 0.7%, p less than 0.01). The reintroduction of the sulfonylurea after insulin withdrawal resulted in a persistent satisfactory long-term control (300 days) in all, but two diabetics responded no more after about 3 and 4 months of clinical remission (good control on sulfonylurea). Both basal and stimulated (iv glucagon and mixed meal) beta-cell secretory activity increased significantly at 3 months and declined thereafter without falling below baseline values. Three months of strict metabolic control seem to restore the sensitivity to sulfonylurea by enhancing beta-cell secretory activity in non-obese type 2 diabetic patients.

Blood Glucose↗