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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the effect of diabetes mellitus on ketone removal rates, Na DL-beta-hydroxybutyrate was administered as a continuous three-hour infusion (3 mg./kg./min.) to healthy volunteers and insulin-dependent diabetics in the postabsorptive state. An additional group of healthy controls received intravenous glucose (50 gm.) or glucose and insulin during the ketone infusion to determine the effect of hyperinsulinemia on ketone removal. Following ketone infusion, total blood ketone levels in the diabetics were twofold greater than in controls (p less than 0.001). The metabolic clearance rate of ketones (MCRk) in the diabetics was reduced by 42% from that of controls (p less than 0.001). In contrast, the calculated production rate of ketones (PRk) in diabetics was not consistently different from that observed in controls. In diabetics with normal PRk, MCRk remained significantly below control values (p less than 0.001). The ketone infusion resulted in a fall in plasma glucose and alanine levels in the normals as well as diabetics. However, the decline in plasma glucose induced by the ketone infusion was five- to sixfold greater in the diabetics than in controls (p less than 0.005) and correlated linearly with the decline in plasma alanine (p less than 0.02). Administration of intravenous glucose during an ongoing ketone infusion in normal subjects resulted in 37 +/- 5% reduction in beta-hydroxybutyrate, but no change in acetoacetate concentration. The decline in beta-hydroxybutyrate was two- to threefold greater than would be expected if glucose had acted solely to inhibit endogenous ketone production. Similar results were observed when hyperinsulinemia without hyperglycemia was produced by simultaneous administration of insulin and glucose. It is concluded that (1) ketone disposal is reduced in diabetes even when ketone production is normal, suggesting the rate of ketone utilization may be a more sensitive index of insulin deficiency than is ketone production; (2) hyperinsulinemia stimulates beta-hydroxybutyrate utilization without influencing acetoacetate concentration; and (3) increased blood ketone levels induced by infusion of Na DL-beta-hydroxybutyrate reduce plasma glucose and alanine concentrations in diabetes. These findings thus support a role for insulin in influencing ketone disposal in normal as well as diabetic man and a role for ketones in influencing substrate availability for gluconeogenesis in diabetes.
Diabetes 1976 Sep
PMID:Effect of diabetes mellitus and insulin on the turnover and metabolic response to ketones in man. 95 5

The insulin response to oral glucose ingestion was measured in six patients with the Zollinger-Ellison (ZE) syndrome, five patients with partial gastrectomy (antrectomy for duodenal ulcer) and six matched normal subjects. The blood glucose curves were similar in ZE-patients and gastrectomized controls and significantly above the glucose concentrations in normal controls. The insulin response was three-doubled in ZE-patients, whereas gastrectomized controls only doubled their response in comparison with the normal subjects. Treatment of a hepatic gastrinoma by streptozotocin infusion into the hepatic artery in a patient with diabetes mellitus and hyperinsulinism almost normalized his glucose tolerance and insulin secretion. The results demonstrate that the ZE-syndrome is associated with increased insulin release. We suggest that the hyperinsulinism partly is a consequence of previous gastric surgery and partly due to the insulinogenic effect of gastrin.
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PMID:Insulin secretion in the Zollinger-Ellison syndrome. 106 42

Two boys and one girl developed persisting hypoglycaemia 12, 24, and 48 hours after birth. Although there was no known history of hereditary diabetes mellitus, the birth weight was high in two cases, and some additional traits of foetopathia diabetica could not be excluded clinically. All had high serum insulin levels with frank hyperinsulinaemia in one case. Glucose tolerance tests also indicated hyperinsulinism. Diazoxide (8 to 27 mg/kg) elevated the blood glucose levels, but did not prevent severe hypoglycaemic episodes. The effects of subtotal pancreatectomy were only transient. The patients have now been kept on permanent diazoxide therapy for 2-4 years at dosages slightly lower than those used before operation. No islet-cell tumour was found at the subtotal pancreatectomy. In all 3 cases, the pancreatic islets were markedly hyperplastic and of irregular shape with the occurrence of large B-cells with giant hyperchromatic nuclei and chromophobe "agranular" or sparsely granulated cells. The predominating kind of islet cells showed tinctorial features of A2-cells but--in the absence of available material set aside for ultrastructural analysis--it could not be settled whether this was a result of a proliferation of A2-cells only or of "type IV cells" as well. Against the background of previously published reports, the present cases serve to illustrate that additional accuracy of diagnosis and classification of neonatal persistent hypoglycaemia requires quantitative information about the structural changes in the pancreatic islet cells, and that this can be obtained from conventional biopsy specimens.
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PMID:Persistent neonatal hypoglycaemia. A clinical and histopathological study of three cases treated with diazoxide and subtotal pancreatectomy. 109 27

The intracisternal administration of insulin (0.2 U./kg.) to anesthetized dogs resulted in an increase of arterial immunoreactive insulin and a decrease of plasma glucose relative to a control injection. The arterial responses were significantly attenuated when the insulin was administered to the cisternum of subdiaphragmatically vagotomized dogs. When cerebrospinal fluid glucose was lowered by injecting pneumococcal neuraminidase intracisternally, no peripheral hyperinsulinemia resulted, indicating that increased spinal fluid insulin and its consequent increase of glucose uptake, rather than decreased spinal fluid glucose, is necessary to elicit the vagally mediated insulin secretion and hypoglycemia. It is hypothesized that increased spinal fluid insulin causes an increased glucose uptake of some glucoregulatory area of the brain and that the elicited reflex is vagally mediated pancreatic insulin secretion.
Diabetes 1975 Oct
PMID:Effect of intracisternal insulin on plasma glucose and insulin in the dog. 110 Apr 59

Ethanol at an average blood concentration of 1 mg. per milliliter enhanced the immediate (first-phase) and prolonged (second-phase) insulin response to an intravenous glucose load in nonfasting normal human subjects. Simultaneously, the glucose disposal rate was increased and the postglucose hypoglycemia was accentuated, resulting in definite hypoglycemic symptoms in some individuals. Oral glucose tolerance was not changed by ethanol administration, but the thirty-minute blood glucose and plasma insulin values were increased, suggesting that alcohol might accelerate the absorption of glucose from the gut. Ethanol given orally during evening hours (1.5 gm. per kilogram) caused a nocturnal hyperinsulinemia and a decrease of blood glucose, but not an actual hypoglycemia. Oral glucose tolerance and plasma insulin response tested the next morning, when ethanol had disappeared from the blood, were not influenced by drinking the previous evening. The K-value of intravenous glucose was increased at this time, however. When alcohol was administered for one week at a dose corresponding to 25 per cent of daily calories and substituting for fat, both the oral and intravenous glucose tolerances were impaired in each subject but the insulin response remained unchaged. In obese nondiabetic subjects, ethanol did not potentiate the early insulin response to intravenous glucose but it increased the second phase of insulin secretion in response to sustained hyperglycemia. In contrast to conditions in nonobese subjects, the glucose disposal rate was not incresed and postglucose hypoglycemia was not accentuated by ethanol in overweight subjects. In insulin-deficient diabetic patients the absent early insulin response could not be restored by ethanol, and the late component of insulin release was little increased by alcohol infusion. Ethanol did not improve the glucose utilization of diabetic patients.
Diabetes 1975 Oct
PMID:Ethanol-induced alterations of glucose tolerance, postglucose hypoglycemia, and insulin secretion in normal, obese, and diabetic subjects. 110 Apr 61

A newborn infant, small for her gestational age with macroglossia and transient insulinopenic diabetes mellitus is described. Two similar cases have been found in the literature. Flat glucose tolerance test results were found in the mother, the mechanism of which was not disclosed; there was no evidence of hyperinsulinism or malabsorption syndrome and the response of plasma growth hormone, and cortisol, and of urinary epinephrine to insulin-induced hypoglycemia was adequate. It is suggested that the triad of intrauterine growth retardation, macroglossia, and transient neonatal diabetes mellitus constitutes a distinct clinical entity. The link to the maternal abnormalities of carbohydrated homeostasis remains speculative.
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PMID:Macroglossia, transient neonatal diabetes mellitus and intrauterine growth failure: a new distinct entity? 111 Aug 57

Factitious hyperinsulinism was suspected in a patient with an 11-year history of insulin-dependent, ketosis-prone diabetes mellitus who began to experience repetitive episodes of "spontaneous" hypoglycemia. Insulin mediation of the hypoglycemia was confirmed by documenting that urinary insulin and total extractable insulin in plasma increased during periods of hypoglycemia. Failure to detect significant amounts of human C-peptide by radioimmunoassay during periods of hypoglycemia or in response to stimulation with glucagon, leucine, or tolbutamide indicated that the insulin was not endogenous. The diagnosis of factitious hyperinsulinism was ultimately proved by the finding of radioactivity in the patient's urine after 131-I Hippuran was added to a vial of insulin found in the patient's room.
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PMID:Plasma C-peptide and diagnosis of factitious hyperinsulinism. Study of an insulin-dependent diabetic patient with "spontaneous" hypoglycemia. 111 42

Thirty-seven cases of neonatal hypoglycaemia were studied at follow-up at the age of 2 6/12-r 9/12 years. Two of them had had hypoglycaemia were stuafter the newborn period, and another patient died in a hypoglycaemic state following surgery at 10 weeks of age. Twenty-three children had oral glucose tolerance tests and intravenous insulin tolerance tests performed. Diabetic glucose tolerance was noted in 3 children. None of them showed symptoms of diabetes mellitus, neither was there any family history of diabetes. One of these patients had experienced hypoglycaemia after the newborn period and responded with hyperinsulinism during the glucose tolerance test. The other hypoglycaemic patient showed an exaggerated insulin release in response to tolbutamide. Deficient serum cortisol response to insulin-induced hypoglycaemia was demonstrated in 7 patients and 6 of these had concomitant minimal growth hormone response. One of these patients also had a diabetic glucose tolerance. None were of short stature. It is probable that a disturbance in the hypothalamic-pituitary-adrenal axis may contribute to an impaired carbohydrate metabolism in some patients with neonatal hypoglycaemia.
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PMID:Endocrinological aspects at follow-up studies in neonatal hypoglycaemia. 113 Jan 86

In vivo studies were undertaken in rats to provide evidence of the neural nature, tentative localization and mode of excitation of the insulin-sensitive central nervous system (CSN) glucoregulator center. In rats under light barbiturate anesthesia minute amounts of insulin injected into the carotid artery resulted in an immediate decrease of the systemic blood sugar. This hypoglycemic action of regional insulinzation of the CSN was lost when the animals were subjected to prolonged, deep barbiturate narcosis. Competitive inhibition of glucose utilization in the CSN region by intracarotid administration of 2-deoxy-D-glucose did not block the systemic hypoglycemic effect of subsequent intracarotid insulin injection. Chronic endogenous hyperinsulinemia produced by daily growth hormone treatment resulted in an insensitivity of the CNS glucoregulator center to exogenous insulin. The ratio of the quantity of the injected insulin and the pre-existent plasma insulin concentration showed direct correlation with the systemic hypoglycemic response that followed intracarotid injection. Present data support the hypothesis that the insulin-sensitive glucoregulator center located in the area supplied by the carotid artery is neural in nature, because of its inhibition by barbiturate anesthesia. The data are compatable with the working hypothesis that the center is located in the hypothalamus, since light cortical barbiturate anesthesia did not, but deep anesthesia did have an inhibitory effect on it. Marked interference by chronic hyperinsulinemia suggests that the receptor center estimates the metabolic status of the animal through means related to physicochemical binding of insulin to specific receptors. However, since our attempt to inhibit glucose utilization in the CNS was without effect on the activity of the center, it appears that the singal for the glucoregulatory impulse is not insulin facilitation of glucose utilization in the receptor area, but another parameter of insulin action.
Diabetes 1975 Apr
PMID:Studies on the nature and mode of action of the insulin-sensitive glucoregulator receptor in the central nervous system. 113

The disappearance rate of intravenously injected insulin was investigated in the serum of 30 women during the third trimester of pregnancy and 6 to 8 weeks post partum, in order to determine whether pregnancy has an influence on insulin kinetics in human subjects. Both women with unimpaired glucose tolerance and those with latent diabetes were included in this study. The disappearance rate of exogenous serum insulin in pregnancy was characterized by a two-compartment model. Multivariate analyses of variance were used to determine whether the estimated parameters of this model during pregnancy differ from those obtained after the puerperium and whether the insulin kinetics are altered when carbohydrate metabolism is disturbed. The kinetics of insulin during pregnancy did not differ from those after pregnancy. Thus, hyperinsulinemia observed in pregnancy cannot be explained by a change in the insulin kinetics. It appears improbable that the insulin-degrading enzyme activities of the placenta participate in degradation of insulin circulating in the maternal blood. A connection between the decline of glucose tolerance during pregnancy and the kinetics of exogenous insulin could not be found.
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PMID:Influence of pregnancy on the kinetics of insulin. 114 34


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