[Therapeutic prospectives in the field of hypertension].
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Biomedical subjects
Publications and source records attributed to U Butturini.
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Two groups of patients affected by idiopathic androgenization have been treated with ethinylestradiol (EE) associated with two different (high and low) dosages of cyproterone acetate (CA); the aim of this study was to evaluate the possible endocrine side effects at the pituitary level. After three and six months of treatment gonadotropins secretion appeared significantly inhibited with higher evidence for LH than for FSH and especially in the patients on high dose of CA. Nevertheless the most impressive finding was represented by the increase in PRL responses to TRH documented when higher doses of CA were employed without significant change in TSH secretion. The Authors suggest that such PRL hyperresponsiveness cannot be completely disregarded in the management of idiopathic androgenization.
Increased plasma insulin and triglycerides and decreased high density lipoprotein concentrations are primary risk factors in the development of coronary artery disease. The aim of the present study was to verify whether there was an independent relationship between plasma insulin levels and both HDL cholesterol and triglyceride in a worker population of 607 subjects, 389 men and 218 women, aged 23-73 years. An oral glucose tolerance test (75 g) was performed. Plasma glucose, insulin, triglyceride and HDL cholesterol were measured at fasting, plasma glucose and insulin were determined also 1 h and 2 h after glucose load. The results, examined separately in men and women documented a significant negative relationship between plasma insulin and HDL cholesterol level, as well as pointing out that both HDL cholesterol and insulin are significantly correlated to degree of hypertriglyceridemia, degree of obesity and level of glucose tolerance. The partial correlation coefficients between HDL cholesterol and plasma insulin levels at fasting in men and post-glucose load in women, demonstrated an independent relationship between increased plasma insulin and decreased plasma HDL concentration. However, the strongest relationship, revealed by partial correlation coefficient analysis, was between the degree of hyperinsulinemia and hypertriglyceridemia.
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The study was designed to evaluate whether the correlation occurring in simple obesity between insulin resistance and peripheral hyperinsulinemia corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the study investigated the relation existing in simple obesity between insulin resistance and insulin metabolism. For these purposes, we measured and correlated: (1) insulin sensitivity, estimated by glucose disappearance rate from plasma after intravenous insulin injection; (2) insulin secretion by the pancreas, estimated by fasting C-peptide levels in peripheral blood; (3) insulin metabolism, estimated by means of C-peptide: insulin molar ratio in peripheral blood. Twenty-five subjects (20 females, five males) aged 21 to 59 years were studied. All were obese and had a normal glucose tolerance. Glucose disappearance rate from plasma after i.v. insulin injection averaged 3.65 +/- 0.42 mg/dl/min (mean +/- s.e.m.). Fasting C-peptide was 0.90 +/- 0.09 nmol/l. Fasting C-peptide: insulin molar ratio averaged 5.94 +/- 0.48. Negative correlations were found between glucose disappearance rates after i.v. insulin injection, ie, insulin sensitivity, and fasting concentrations of both insulin (r = -0.806, P less than 0.001) and C-peptide (r = -0.525, P less than 0.01). A positive relationship was found between glucose disappearance rate from plasma after i.v. insulin injection and fasting C-peptide: insulin molar ratio, ie, insulin metabolism (r = 0.707, P less than 0.001). We conclude that in simple obesity insulin overproduction by the pancreas is negatively related to insulin resistance, and insulin resistance and impaired insulin metabolism are strictly related phenomena.
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Plasma levels and renal uptake of gastrin were determined in ten dogs submitted to complete liver devascularization in order to induce an acute liver failure. Renal function was evaluated by renal plasma flow (RPF) and glomerular filtration rate (GFR) determinations. Liver devascularization was obtained by end-to-side porto-caval shunt (PCS) followed by temporary clamping of the hepatic artery. PCS alone did not affect renal function and renal ability to remove gastrin; after hepatic ischemia, both RPF, GFR and renal extraction of gastrin showed an abrupt decrease. At the end of the period of hepatic ischemia 5 dogs were submitted to glucose infusion, in consideration that: i) glucagon is able both to affect gastrin release and renal hemodynamics, and ii) hypoglycemia that develops after liver failure releases elevated amounts of glucagon. The renal handling of gastrin was not related to glucagon plasma levels, though the higher gastrin levels occurred at the lower glucagon concentrations. These data suggest that in acute liver failure there is a striking decrease of the renal clearance of gastrin associated with the impairment of kidney function. Furthermore, in this pathological condition plasma gastrin levels are affected by blood glucose concentrations through its effect on plasma glucagon levels.
The ability of metformin to prevent carbohydrate-induced hypertriglyceridemia was studied in fructose fed rats. The results indicated that plasma triglycerides were approximately 50% reduced in the drug treated rats and the reduction was associated with lowered very low density lipoprotein-triglyceride secretion rates and plasma insulin levels. Since the drug does not affect the fructose intestinal absorption, it did not prevent normal rate of weight gain. These results provide further evidence for the existence of a causal relationship between plasma TG concentration and plasma insulin concentration; metformin is able to modify both these variables likely affecting primarily the ambient insulin level.
Exaggerated insulin response to oral glucose was demonstrated in peripheral blood of patients with chronic hepatic diseases. High peripheral insulin levels may be the result of pancreatic hypersecretion or decreased hepatic removal of insulin. The simultaneous assay of insulin and C-Peptide concentrations in peripheral blood enables the determination of both beta-cell activity and hepatic fractional insulin extraction. We have measured peripheral insulin and C-Peptide levels during OGTT in a group of subjects with chronic active hepatitis (CAH). These subjects showed glucose levels and incremental areas significantly higher than controls, but still in the upper range of normality. Insulin response to oral glucose was significantly greater in CAH patients than in controls, whereas C-Peptide levels and areas were quite similar in the two groups. The C-Peptide to insulin molar ratios before and after glucose, and the relations between C-Peptide and insulin incremental areas were lower in CAH patients than in controls. We conclude that the peripheral hyperinsulinemia observed in subjects with CAH is due to diminished insulin removal by the diseased liver rather than pancreatic hypersecretion.
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In the present study insulin and C-peptide responses to oral glucose as well as C-peptide to insulin ratios and relations were evaluated in 10 nondiabetic obese female subjects with reactive hypoglycemia and in 10 age- and weight-matched controls. Insulin levels and incremental areas did not differ significantly in the two groups, whereas C-peptide concentrations and incremental areas were significantly higher in the obese group with reactive hypoglycemia. C-peptide to insulin molar ratio increments after glucose load as well as relations between incremental areas of the two peptides were significantly higher in obese subjects with reactive hypoglycemia than in controls. Our results suggest that B-cell response to oral glucose as well as insulin uptake by the liver in obese subjects with reactive hypoglycemia are greater than in controls.
The aim of the present study was to investigate the secretion and the hepatic removal of insulin in a group of 14 unaffected offspring of 14 type 2 (noninsulin-dependent) diabetic couples compared to 14 healthy subjects without family history of diabetes mellitus. The two groups, each consisting of 5 obese and 9 nonobese subjects, were carefully matched for sex, age, and body weight. We examined glucose, insulin, and C-peptide levels, as well as C-peptide to insulin ratios and relations during the oral glucose tolerance test. Glucose concentrations and incremental areas were similar in the two groups, as well as insulin and C-peptide levels and areas. C-peptide to insulin molar ratios, both in fasting state and after glucose load, as well as relations between C-peptide and insulin incremental areas were not different. Our results suggest that the healthy offspring of type 2 diabetic couples have a normal response of beta-cell to oral glucose as well as a normal removal of insulin by the liver.
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.
In order to establish whether cholinergic receptors mediate GH secretion induced by TRH in insulin-dependent diabetes, 10 patients were treated with pirenzepine, an anticholinergic agent, and tested with TRH. Basal concentrations of GH were elevated in these patients and 8 of 10 patients responded to TRH with a significant rise in GH levels. Pretreatment with pirenzepine (40 mg given iv 10 min before TRH) suppressed the TRH-induced GH rise. Pirenzepine had no effect on TRH-induced TSH release. This finding suggests that a cholinergic mechanism is involved in the paradoxical response of GH to TRH in diabetic patients.
Insulin and C-peptide levels in peripheral blood in the fasting state and after an oral glucose load were measured in 65 nondiabetic, obese subjects and 65 age- and sex-matched nondiabetic normal weight subjects. Fasting insulin and C-peptide levels were significantly higher in obese than in nonobese subjects, whereas 1 and 2 h after the oral glucose load only insulin concentrations were significantly higher in the obese subjects. C-peptide to insulin molar ratios, as well as the relation between the incremental areas of the two peptides, were used as relative measures of hepatic insulin extraction. In the fasting state the ratios between C-peptide and insulin were similar in obese and nonobese subjects, whereas after glucose they were significantly lower in the obese individuals. Similarly, the relations between C-peptide and insulin incremental areas were significantly lower in obese than in nonobese subjects. The comparison of the corresponding plasma levels and areas of C-peptide and insulin after glucose showed that for the same C-peptide value, the insulin value was higher in the obese group. Last, in obese subjects the parameter used as an estimate of hepatic removal of insulin after oral glucose inversely correlated with the fasting insulin concentration and the insulin incremental area after glucose. These results suggest that in obesity peripheral hyperinsulinemia depends on pancreatic hypersecretion of insulin in the fasting state and impaired hepatic insulin metabolism after oral glucose loading.
Only few patients (3,8%) affected by ANLL survive for more than 3 years from the time of diagnosis. In the present study the Authors try to determine which clinical and haematological factors can determine long-terme survival. The Authors describe the case of a male patient (25 years old) affected by ANLL (M2), who became and is still now a long-survivor (80 months from 1th complete remission). He has been treated with DNB, ARA-C and TG (TRA schedule) for two cycles. After CR he refused consolidation and reinduction therapy and was treated only with 6-MP and MTX for 3 years, as maintenance chemotherapy. The Authors suggest that important factors for a favourable prognosis are early diagnosis and young age. A relatively high number of platelets can be correlated with a good prognosis.
The aim of the present study was to investigate the secretion and hepatic removal of insulin in the healthy offspring of type 2 (non-insulin-dependent) diabetic subjects. For this purpose, we examined the insulin and C-peptide responses to a 75 g oral glucose tolerance test in a group of 55 healthy subjects each having one parent with type 2 diabetes mellitus, and in a group of 55 individuals without a family history of diabetes. All the 110 subjects in the study were ambulatory volunteers, in good general health, and with normal glucose tolerance. The two groups were carefully matched for sex, age, and body weight. Glucose and insulin concentrations as well as incremental areas were similar in the two groups. C-peptide levels and incremental areas were almost identical. C-peptide to insulin molar ratios both in fasting state and after glucose load, as well as relations between C-peptide and insulin incremental areas did not differ in the two groups. In conclusion, the healthy offspring of only one non-insulin-dependent diabetic parent show a normal beta-cell response to glucose, and normal removal of insulin by the liver.
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.