Michele Muggeo

Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment

Arginine-induced insulin and glucagon secretion preceding and following clofibrate treatment was studied in 13 patients with endogenous hypertriglyceridemia. A positive correlation was demonstrated between fasting insulin and triglyceride levels and between the fasting insulin/glucagon molar ratio and triglyceride levels. In patients with endogenous hypertriglyceridemia, anginine infusion induced a significantly increased glucagon response with respect to that found in controls. No correlation was found to exist between glucagon and free fatty acids (FFA) or between glucagon and triglyceride levels. The same lack of correlation was found in normal subjects rendered hypertriglyceridemic by means of Intralipid infusion, which did not modify the fasting glucagon-like immunoreactivity (GLI) or the GLI response to arginine. Clofibrate treatment induces a triglyceride reduction (incrementTG) which is correlated with the reduction in the insulin/glucagon molar ration (incrementI/G). After clofibrate treatment there is also a significant reduction in fasting GLI levels and in the insulin response to arginine, and an increase in the glucagon response. Clofibrate could exercise its hypolipidemic effect by modifying the relationship between insulin and glucagon levels.

Bromocriptine acute effect on insulin, glucagon and growth hormone levels in acromegalic patients.

It has been shown that L-dopa or dopamine administration influences glucose metabolism, as well as insulin and glucagon release in man. In the present study, the effect of bromocriptine (CB-154), a long-acting dopamine agonist, on insulin, glucagon and growth hormone secretion in 32 acromegalic patients was investigated. Glucose, insulin and plasma glucagon levels were not modified following administration of bromocriptine or placebo. Moreover, plasma GH levels were decreased by more than 50% in 18 of the 32 acromegalics. Mean GH levels were significantly lower with respect to levels observed following placebo at 60 min to the end of the test (p < 0.001). Administration of a double dose of CB-154 (5 mg po) one hour before arginine test did not affect insulin or glucagon secretion with respect to levels observed during arginine alone. In addition, there was a fall in GH levels similar to that observed following administration of bromocriptine alone. These findings suggest that bromocriptine in itself does not exert a direct action on insulin and glucagon release. Improvement in glucose tolerance and reduction in insulin secretion observed following prolonged CB-154 treatment in acromegalic patients are probably due to a simultaneous inhibition of GH secretion or to other peripheral effects of bromocriptine.

The influence of nicotinamide on the urinary excretion of tryptophan metabolites in Hodgkin's disease.

Abstract The urinary excretion of tryptophan metabolites was studied in 10 patients with Hodgkins disease. As previously found, kynurenine, 3-hydroxykynurenine and 3-hydroxyanthranilic acid were spontaneously excreted in abnormally high amounts, appearing to be a constant characteristic in patients with Hodgkins disease. Tryptophan loading produced an abnormal excretion of 10 metabolites in all, and normal excretion was only partially restored by treatment with nicotinamide administration before a second tryptophan test in the same patients. The effect of nicotinamide on the excretion pattern appeared to differ qualitatively and quantitatively from that obtained using vitamin B6 administration. These data show the existence, in Hodgkins disease, of a deficiency of nicotinamide-dependent enzymes acting on the tryptophan → nicotinic acid pathway, besides that correlated to vitamin B6.

Growth hormone response to insulin and to arginine in patients with familial hypercholesterolaemia.

Human growth hormone (HGH) response to i.v. insulin (0.1 U/kg body weight) and arginine infusion (25 g of L-arginine for 30 min) was studied in 9 patients (5 males and 4 females) with primary familial hypercholesterolaemia and belonging to 4 families. Mean age was 28 +/- 2 years (range 18-36) and body weight was less than 105% of ideal body weight. Glucose tolerance and insulin response to oral glucose were normal in all patients. HGH release after insulin and after arginine was slightly increased as compared to 21 normal controls, but the differences were not significant. Insulin and glucagon response to arginine in these patients was within the normal range. Plasma glucose and free fatty acids were normal after both insulin and arginine. Moreover, no significant correlation was found between fasting cholesterol and HGH peaks after insulin and after arginine, nor between cholesterol and insulin and glucagon responses. Despite marked hyperlipidaemia, HGH-deficient patients examined by other authors never present signs of atherosclerotic disease. Our data suggest that HGH, in the presence of elevated cholesterol levels, might play an important role in the development of atherosclerotic lesions.

Insulin secretion in hyperlipoproteinemias.

SummaryInsulin secretion has been evaluated after oral glucose loading and other stimuli (tolbutamide, glucagon, arginine and i.v. glucose) in a group of 3 patients with familial hyperchylomicronemia (Fredrickson’s Type I), 33 patients with primary hypercholesterolemia (Fredrickson’s Type II) and 89 patients with endogenous hypertriglyceridemia. In familial hyperchylomicronemia glucose tolerance and insulin secretion were normal. In patients with familial hypercholesterolemia the increased insulin secretion is conditioned by overweight. In hypertriglyceridemic patients no significant correlation has been observed after glucose loading between basal insulin and plasma triglycerides and between insulin response (insulin area) and plasma triglyceride levels. Mean insulin response to oral glucose was significantly increased in hypertriglyceridemic patients with normal glucose tolerance and still more in hypertriglyceridemic patients with chemical diabetes. A significant positive correlation has been found between overweight and insulin response after oral glucose in the hypertriglyceridemic patients with normal glucose tolerance. The insulin response after the other stimuli was not significantly different from that of the controls. In conclusion, in primary familial hypercholesterolemia, insulin secretion was increased after oral glucose, with normal glucose tolerance; overweight only partially explained the increased insulin response. In endogenous hypertriglyceridemia, plasma triglycerides were not related to the degree of insulin response after oral glucose. Overweight is related to insulin response only when glucose tolerance is still normal, but with the appearance of a diabetic state, insulin secretion seems to be conditioned by the reduced glucose tolerance. Increased insulin secretion seems to be the first alteration of glucose homeostasis, even in the presence of normal glucose tolerance.

Effects of clofibrate treatment on arginine-induced insulin secretion in endogenous hypertriglyceridemia

Arginine-induced insulin secretion was evaluated in 13 patients with endogenous hypertriglyceridemia (Fredricksons Type IV) before and after a two-month period of Clofibrate therapy. Clofibrate reduced triglyceride, cholesterol and FFA levels by 68, 28 and 15% respectively and provoked a significant reduction in arginine-induced insulin secretion without modifying glucose response. Arginine-induced insulin secretion was also studied in 11 normal subjects during saline and intralipid infusions. Glucose and insulin basal values, and glucose and insulin response to arginine infusion were not influenced by Intralipid infusion in these controls. These results confirm that clofibrate reduces insulin secretion thereby contributing to decreased serum triglyceride levels.

Glucagon and insulin secretion in potential diabetes.

SummaryInsulin and glucagon have been studied in 20 subjects (both of the subjects’ parents were diabetic or in case of only one diabetic parent, the other showed a first degree familiarity of diabetes): 10 showed normal glucose tolerance (‘true prediabetics’) and 10 impaired glucose tolerance (‘genetic chemical diabetes’). Mean insulin response to oral (100 g) and i.v. glucose load (200 mg/kg followed by 20 mg/kg/min for 60 min) and to arginine infusion (25 g in 30 min) was normal in the prediabetics and delayed and higher in the subjects with chemical diabetes as compared to the control group. Glucagon response to arginine was higher, but not significantly, in prediabetics and in subjects with chemical diabetes. In both of these groups glucagon suppression by glucose was not observed. The insulin/glucagon molar ratio was significantly reduced after glucose infusion in these two groups. No correlation was found between insulin and glucagon secretion after arginine or glucose. A possible alteration in the mechanism controlling glucagon secretion even in the earliest phases of diabetes is suggested.

Glucagon and Hypertriglyceridemia

The authors report the results of their studies on glucagon secretion in human endogenous hypertriglyceridemia and on its effects in hyperlipemic patients and in isolated rat liver.

Relazione Tra Metabolismo del Triptofano E Vitamina B6 E Nicotinamide in Pazienti Affetti da Morbo di Hodgkin

Riassuntoè stata studiata l’escrezione urinaria dei metaboliti del triptofano in 24 pazienti con morbo di Hodgkin suddivisi in tre gruppi. La somministrazione di vitamina B6 al primo gruppo ridusse l’escrezione urinaria dei metaboliti, dopo carico di L-triptofano (100 mg/kg), dal 24,1% al 13,3% (controlli 6,7%). Il trattamento con nicotinamide del secondo gruppo produsse una riduzione dei metaboliti dal 19,4% al 9,5%. La somministrazione contemporanea di queste due vitamine nel terzo gruppo normalizzö l’alterato quadro escretorio (dal 23,6% al 7,9%). Tuttavia l’effetto délie due vitamine apparve solo transitorio. Questi dati mostrano l’esistenza nel morbo di Hodgkin di un difetto di due gruppi di sistemi enzimatici, uno B6-dipendente e l’altro nicotinamide-dipen-dente.SummaryThe urinary excretion of tryptophan metabolites was studied in 24 patients with Hodgkin’s disease divided in three groups. Vitamin B6 administration to the first group reduced urinary excretion of metabolites after L-tryptophan loading (100 mg/kg) from 24.1 % to 13.3 % (normal 6.7%). Nicotinamide administration to the second group caused a decrease of the metabolites from 19.4% to 9.5%. The simultaneous treatment of these two vitamins in the third group corrected completely the abnormal excretory picture (from 23.6 % to 7.9 %). However, the effect of the two vitamins appeared only transitory. These data show the existence in Hodgkin’s disease of a failure of two groups of enzymic systems, one Be-dependent and the other nicotinamide-dependent.

The influence of simultaneous administration of vitamin B6 and nicotinamide on tryptophan metabolism in Hodgkin's disease

Abstract The urinary excretion of tryptophan metabolites was studied in 10 patients with Hodgkins disease after tryptophan loading with or without simultaneous administration of vitamin B 6 and nicotinamide. The treatment of these two vitamins corrected completely the abnormal excretory picture (from 23.6% to 7.9%), but with transitory influence. These data show the existence in Hodgkins disease of a failure of two groups of enzymic systems, one B 6 -dependent and the other nicotinamide-dependent.