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

Leptin can be considered as a peripheral signal which informs the centers about the mass of energy stores. Studies done on the human adult population have demonstrated that degree of adiposity and insulin levels play a major role as determinants of leptin circulating levels. The aim of this study was to evaluate which factors may influence leptin levels at birth. We examined the role played by baby size and by the metabolic environment the fetus was exposed to during pregnancy. We considered 85 newborns from normal (n = 60), gestational (GDM, n = 17) and pregestational (IDDM = 8) diabetes mellitus mothers. At delivery, blood was taken from the umbilical cord vein. Babies from normal and GDM mothers were subdivided into AGA (appropriate for gestational age) and LGA (large for gestational age). There was no difference in leptin levels between babies from normal or GDM mothers belonging to the same weight category, but leptin levels were always higher in LGA than in AGA newborns, and highly correlated with birth weight (r = 0.34, P = 0.001). Moreover, IDDM mothers gave birth to newborns with significantly higher levels of leptin and insulin when compared with normal and GDM mothers. Diabetes of both GDM and IDDM mothers was clinically well controlled (HbA1c was 4.0 and 7.2, respectively). The correlation between leptin and insulin was significant only when newborns from IDDM mothers were included in the regression analysis (r = 0.39, P = 0.0002). Our results suggest that degree of adiposity is one of the main regulators of leptin concentration in the human newborn and that babies exposed to an altered, though clinically controlled, metabolic environment, as in IDDM mothers, have increased levels of leptin.
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PMID:Plasma leptin levels in newborns from normal and diabetic mothers. 980 27

The regulation of leptin secretion is complex and not entirely understood in humans. Insulin has been shown to stimulate leptin secretion in humans, whereas in vitro data suggest that catecholamines inhibit leptin secretion. The present studies were therefore undertaken to examine the leptin response to hyperinsulinemia in the presence and absence of elevated plasma levels of endogenous catecholamines in humans. Leptin concentrations were determined during both a euglycemic and hypoglycemic hyperinsulinemic clamp study in 10 normal and 10 type I diabetic subjects. Serum leptin increased during the hyperinsulinemic euglycemic clamp in normal (from 6.1 +/- 0.9 to 7.2 +/- 1.1 ng/dl, p = 0.003) and diabetic subjects (from 6.2 +/- 1.4 to 7.8 +/- 1.8 ng/dl, p = 0.001). During hyperinsulinemic hypoglycemia leptin concentrations increased significantly in type 1 diabetic patients (from 5.6 +/- 1.1 to 7.6 +/- 1.7 ng/dl, p = 0.003) but remained unaltered in normals (from 5.5 +/- 0.7 to 5.7 +/- 0.9 ng/dl, p = 0.7). During hypoglycemia in all subjects the increase in leptin was negatively correlated with the increase in epinephrine (r = 0.60, p = 0.005) and positively with the decrease in free fatty acids (r = 0.71, p = 0.003). In conclusion our results indicate that catecholamines play a suppressive role in the regulation of leptin secretion.
Exp Clin Endocrinol Diabetes 1998
PMID:Evidence for inhibition of leptin secretion by catecholamines in man. 983 8

Diabetes mellitus is a common disease in older people, with almost 50% of Type 2 diabetic patients being over 60 years of age; despite this, half of older people with frank diabetes are not diagnosed. While insulin resistance is common in older people, large numbers also have impaired insulin secretion. Age, body habitus and physical activity all play a role in the pathogenesis of hyperglycaemia associated with diabetes mellitus. Leptin levels relate to insulin resistance in older people and amylin secretion is associated with delayed return of glucose levels to baseline. Depression, impaired cognitive function, and lack of recognition of thirst and subsequent dehydration are important factors to be taken into account in the management of older diabetic patients, who may also have impaired physical function, an increased rate of injurious falls, and increased prevalence of pressure ulcers, amputations and tuberculosis. Hyperglycaemia can result in a decreased pain threshold and incontinence. Dietary management plays less of a role in older diabetic patients but exercise, with a particular emphasis on balance and stability, is an important component of the management and treatment of older diabetic patients. The use of metformin as a treatment should be avoided in patients over 80 years of age because of declining kidney function. Insulin therapy is an option but as hypoglycaemia is related to advancing age, patients should be monitored carefully for the development of hypoglycaemia. Care providers also play an important role in the management of older people with diabetes mellitus. Glycaemic control can be obtained with minimal side-effects in most older diabetics including those patients in nursing homes.
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PMID:The elderly Type 2 diabetic patient: special considerations. 986 91

The effects of the adipocyte-derived hormone leptin on glucose metabolism in hepatocytes were investigated. Incubation of hepatocytes from Wistar rats with leptin for 16 h caused a dose-dependent increase in incorporation of [14C]glucose into glycogen, with a maximal effect at 30 nmol/l leptin. This effect of leptin was observed over a range of glucose concentrations (10-25 mmol/l) and was associated with stimulation of net glycogen deposition. It was not counteracted by mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, indicating that it is not due to increased gluconeogenic flux. Leptin also enhanced the short-term stimulation of glycogen synthesis by insulin. These effects of leptin were associated with inhibition of phosphorylase a, which occurred after 4 h of exposure to leptin. Culture with leptin for 16 h did not affect the activities of glucose-6-phosphatase or glucokinase or the activation state of glycogen synthase. Leptin did not affect glycolysis determined from the detritiation of [3-(3)H]glucose. The inhibitory effects of leptin on phosphorylase a were counteracted by short-term incubation with glucagon but were additive with the inhibitory effects of insulin and also with the inhibition caused by resorcinol (25 pmol/l), which inhibits phosphorylase kinase by a mechanism analogous to the antidiabetic drug proglycosyn. These results show that leptin has additive effects with insulin in inhibiting phosphorylase and stimulating glycogen storage in hepatocytes, indicating that these hormones act by separate but convergent mechanisms. It is concluded that the primary action of leptin in hepatocytes is to enhance glycogen storage. This may be an important compensatory mechanism for the inhibition of insulin secretion.
Diabetes 1999 Jan
PMID:Leptin enhances glycogen storage in hepatocytes by inhibition of phosphorylase and exerts an additive effect with insulin. 989 17

The mechanisms underlying the increase in energy expenditure during leptin treatment are not clear. We recently showed that a 5-h intravenous or intracerebroventricular infusion of leptin elevated basal glucose uptake in skeletal muscle (SM) and brown adipose tissue and increased whole-body glucose turnover in C57Bl/6J mice (Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ: Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389:374-377, 1997). We extended the previous study by measuring steady-state levels of uncoupling protein (UCP)-2 mRNA and UCP-3 mRNA in white adipose tissue (WAT) and SM. Leptin by intravenous or intracerebroventricular infusion for 5 h was associated with a decrease in UCP-2 mRNA in WAT (47-52%) and UCP-3 mRNA in SM (33-37%). Because overexpression of UCP-2 or UCP-3 can depolarize the inner mitochondrial membrane, suppression of UCP-2 mRNA and UCP-3 mRNA may in fact lower respiratory demands in WAT and SM. This is consistent with the parallel suppression of cytochrome oxidase subunit IV (COX-IV) mRNA in WAT (35-39%) after leptin infusion. COX-IV mRNA in SM did not respond to acute leptin treatment. Mitochondrial inorganic phosphate carrier (P1C) mRNA was also suppressed in WAT (33-35%) by either method of leptin infusion, but only intravenous infusion of leptin reduced P1C mRNA in SM (40%). Denervation suppressed mRNA levels for UCP-2 (49%), UCP-3 (36%), and COX-IV (59%) and eliminated the acute response to leptin in SM. The comparable response to leptin under intravenous or intracerebroventricular infusion and the loss of responsiveness after denervation strongly suggest that the acute effects of leptin involve central signaling pathways.
Diabetes 1999 Jan
PMID:Downregulation of uncoupling protein 2 mRNA in white adipose tissue and uncoupling protein 3 mRNA in skeletal muscle during the early stages of leptin treatment. 989 33

Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels. Here we examine pancreatic islets isolated from pancreata of human donors for their responses to leptin. The presence of leptin receptors on islet beta-cells was demonstrated by double fluorescence confocal microscopy after binding of a fluorescent derivative of human leptin (Cy3-leptin). Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose. Intracellular calcium responses to 16.7 mM glucose were rapidly reduced by leptin. Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose. Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose. These findings demonstrate direct suppressive effects of leptin on insulin-producing beta-cells in human islets at the levels of both stimulus-secretion coupling and gene expression. The findings also further indicate the existence of an adipoinsular axis in humans in which insulin stimulates leptin production in adipocytes and leptin inhibits the production of insulin in beta-cells. We suggest that dysregulation of the adipoinsular axis in obese individuals due to defective leptin reception by beta-cells may result in chronic hyperinsulinemia and may contribute to the pathogenesis of adipogenic diabetes.
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PMID:Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. 1002 36

The present study was performed to determine the effects of central administration of leptin on food intake and sympathetic nervous system activity in a nonrodent species, the rhesus monkey. Peripheral administration of leptin at doses (1 and 3 microg/kg, s.c.) that produced increments of circulating leptin concentrations within a physiological range did not inhibit food intake over the subsequent 3 days. In contrast, leptin (1 microg/kg, intracerebroventricularly) had no acute effect on food intake, but caused a significant and sustained suppression (40-50%) of food intake during the entire following day (P < 0.01). In addition, circulating norepinephrine levels increased by 55 +/- 16% (P < 0.02) 1 h after intracerebroventricular leptin administration, but did not increase after artificial cerebrospinal fluid administration. These results indicate that leptin can provide a signal to the central nervous system that decreases food intake in primates and in addition acutely activates the sympathetic nervous system. However, the results showing an acute increase in circulating leptin concentrations after peripheral administration of human leptin suggest that in primates, increases in circulating leptin within the physiological range do not acutely regulate food intake. Leptin may be more important in regulating food intake when there are sustained changes in circulating concentrations of leptin (e.g. with obesity, prolonged energy restriction, or diabetes).
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PMID:Central administration of leptin inhibits food intake and activates the sympathetic nervous system in rhesus macaques. 1002 42

Leptin, the product of ob gene is secreted by adipose tissue. It is believed that leptin plays an important role in energy balance. The secretion of leptin by adipose tissue is influenced by insulin. The aim of the present study was the estimation of plasma leptin concentrations in patients with type 2 diabetes mellitus. The study was carried out in 21 diabetic obese patients (BMI > 27.5), 8 diabetic patients with BMI < 27.5, 24 obese patients with normal glucose tolerance (BMI > 27.5) and 10 patients from the control group (BMI < 27.5). The mean leptin concentration in obese diabetic patients was 22.5 + 6.5 ng/ml and was not significantly different from that in obese patients without diabetes (24.1 + 10.3 ng/ml) but differed markedly in comparison to the normal weight diabetic patients (7.9 + 4.3 ng/ml, p < 0.01). Plasma leptin concentration correlated significantly and positively with BMI and fasting insulin in all studied groups. There was no significant correlation between leptin and glycated hemoglobin, total cholesterol and triglycerides. We conclude that serum leptin concentrations in patients with type 2 diabetes depends mainly on the amount of body fat.
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PMID:[Levels of leptin in plasma of patients with type 2 diabetes]. 1008 1

Leptin administration has been shown to increase renal, adrenal, and lumbar sympathetic nerve activity. However, this generalized sympathoexcitatory activity is not always followed by an increase in arterial pressure. The present study tested the hypothesis that leptin induces a release of nitric oxide (NO) that opposes the pressor effect of sympathoexcitation. The effect of intravenous administration of leptin (10, 100, and 1,000 microg/kg body wt) or vehicle on blood pressure (BP), heart rate (HR), and serum nitrite/nitrate concentrations of anesthetized Wistar rats was examined. At 90 min after injection, the three leptin doses tested increased serum NO concentrations 20.5, 33.1, and 89.5%, respectively (P < 0.001 vs. baseline). The effect of leptin on NO concentrations was significantly dose-dependent on linear trend testing (P = 0.0001). In contrast, leptin did not change serum nitrite/nitrate concentrations of fa/fa rats. Leptin administration to Wistar rats under NO synthesis inhibition (N(omega)-nitro-L-arginine methyl ester [L-NAME]) produced a statistically significant increase (P < 0.05) in both systolic BP and mean arterial pressure as well as in HR (P < 0.01). Injection of leptin into rats with pharmacologically induced ganglionic blockade (chlorisondamine) was followed by a decrease in BP and HR to values significantly lower (P < 0.01) than those observed with chlorisondamine treatment alone. The leptin-induced hypotension observed in the setting of ganglionic blockade was blocked by L-NAME. These findings raise the possibility that the leptin-induced release of NO may contribute to the homeostasis of BP.
Diabetes 1999 Apr
PMID:Pivotal role of nitric oxide in the control of blood pressure after leptin administration. 1010 10

Since the discovery of leptin, a boom of scientific knowledge became available about the OB-protein gene and its role and significance in weight regulation. Both from animal and human research data, serum leptin can probably be considered as one of the best biological markers to reflect total body fat, and this finding is true over a wide range of body mass indexes (BMIs) and in different pathologies: in normal weight, anorexic and obese subjects; in non insulin-dependent diabetes mellitus (NIDDM) patients, PCO women, Prader-Willi children and subjects with hypogonadism and growth hormone deficiency. Gender differences clearly exist, probably related to sex hormone differences, and from fat distribution studies it could be shown that subcutaneous fat is much more related to serum leptin concentrations than visceral fat: also leptin messenger-RNA (m-RNA) expression is significantly higher in subcutaneous fat from human obese subjects. Leptin is not only correlated to a series of endocrine parameters such as insulin, insulin-like growth factor, (IGF) and SHBG, it seems involved as a mediator in some endocrine mechanisms (onset of puberty, insulin secretion, etc) as well. Weight loss will reduce human leptin concentrations, whereas the administration of human recombinant leptin seems to show only limited effects.
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PMID:Clinical endocrinology of human leptin. 1019 59


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