Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased synthesis rate of fibrinogen, an independent risk factor for cardiovascular disease, was recently reported in obese insulin-resistant female adolescents with chronic elevated nonesterified fatty acids (NEFA). It is unknown whether a short-term change of NEFA concentrations controls hepatic fibrinogen synthesis. Therefore, 10 healthy male volunteers (24.5 +/- 3.3 yr, body mass index 23.5 +/- 2.9 kg/m2) were investigated in random order under basal and elevated NEFA for 8 h. Leucine metabolism, the fractional synthesis rates (FSR) of plasma fibrinogen, and endogenous urea production rates were measured during primed, continuous infusion of [1-13C]leucine and [15N2]urea, respectively. Plasma alpha-[13C]ketoisocaproic acid and [15N2]urea enrichment values were measured with GC-MS. Plasma fibrinogen was isolated with the beta-alanine method, and fibrinogen-related [13C]leucine enrichment was analyzed by GC-CIRMS. Lipofundin infusion and subcutaneous heparin tripled NEFA and triglycerides in the tests. Plasma glucose, circulating insulin, human C-peptide, and plasma glucagon were not changed by the study procedure. Fibrinogen FSR were significantly lower in tests with NEFA elevation (18.44 +/- 4.67%) than in control tests (21.48 +/- 4.32%; P < 0.05). Plasma fibrinogen concentrations measured were not significantly different (NEFA test subjects: 1.85 +/- 0.33, controls: 1.97 +/- 0.54 g/l). Parameters of leucine metabolism, such as leucine rate of appearance, leucine oxidation, and nonoxidative leucine disposal, were not influenced by NEFA elevation, and endogenous urea production remained unchanged. NEFA contributes to short-term regulation of fibrinogen FSR in healthy volunteers under unchanged hormonal status, leucine metabolism, and overall amino acid catabolism. Its contribution might be of relevance at least after fat-rich meals, counteracting by reduction of FSR the blood viscosity increase implied by hyperlipidemia.
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PMID:Effects of fatty acids on hepatic amino acid catabolism and fibrinogen synthesis in young healthy volunteers. 1279 2

Increased postprandial lipemia is a risk marker of cardiovascular disease (CVD). While moderate alcohol drinking is associated with a reduced risk of CVD in nondiabetic and type 2 diabetic patients, it is also known that alcohol increases postprandial triacylglycerol levels. The incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are important hormones from the gut that enhance nutrient-stimulated insulin secretion. Their responses to a moderate alcohol dose in type 2 diabetes have not previously been studied. We sought to determine how alcohol influences postprandial lipid and incretin levels in patients with type 2 diabetes when taken in combination with a fat-rich mixed meal. Eleven patients with type 2 diabetes ingested on 3 separate days in random order 3 different meals containing: 100 g butter alone or 100 g butter in combination with 40 g alcohol and 50 g carbohydrate, or 100 g butter and 120 g carbohydrate. The meal with alcohol and 50 g carbohydrate was isocaloric to that of 120 g carbohydrate. Triacylglycerol levels were measured after separation by ultracentrifugation into a chylomicron-rich fraction with Svedberg flotation unit values (Sf) > 1,000, and a chylomicron-poor fraction with Sf < 1,000. Supplementation of a fat-rich mixed meal with alcohol in type 2 diabetic subjects suppressed GLP-1 early in the postprandial phase and increased the late triacylglycerol responses compared with the 2 other meals. In the chylomicron-rich fraction, both triacylglycerol and cholesterol were increased by alcohol. No significant differences in high-density lipoprotein (HDL)-cholesterol levels were seen. Isocaloric amounts of carbohydrate and alcohol suppressed equally the postprandial free fatty acid levels, but carbohydrate increased the postprandial glucose, GIP, and insulin levels the most. Early in the postprandial phase, alcohol suppresses the incretin responses and increases the late postprandial triacylglycerol levels in type 2 diabetic patients. Whether this reflects an alcohol-induced suppression of the incretin response, which adds to the alcohol-induced impairment of triacylglycerol clearance in type 2 diabetic patients, remains to be elucidated.
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PMID:Ethanol with a mixed meal decreases the incretin levels early postprandially and increases postprandial lipemia in type 2 diabetic patients. 1468 46

Acromegaly is associated with insulin resistance and an increased incidence of cardiovascular disease. However, it remains unclear to what extent the effects of growth hormone (GH) excess on cardiovascular morbidity and mortality are mediated through insulin resistance versus through other direct or indirect effects of GH. Adequate control of GH excess by surgery or pharmacologic interventions is associated with decreased insulin resistance, reflected in decreased plasma insulin levels and fasting glucose levels or improved glucose tolerance. Despite divergent effects of both somatostatin and somatostatin analogs on GH, insulin and glucagon secretion, and glucose absorption, treatment with the somatostatin analogs octreotide and lanreotide has only limited effects on glucose metabolism. However, glucose sensitivity has only been formally examined using a hyperinsulinemic euglycemic clamp in a minority of these studies. Treatment with the GH-receptor antagonist pegvisomant ameliorates insulin sensitivity, reflected in decreased fasting plasma insulin levels and fasting glucose levels. Nonetheless, the effect of pegvisomant on glucose sensitivity has not been formally tested by hyperinsulinemic clamp conditions. In acromegaly, preliminary observations on new octreotide analogs with greater specificity for somatostatin-receptor subtypes indicate that these compounds achieve better control of GH hypersecretion than octreotide, but may also negatively influence insulin release. Assessment of insulin secretion and glucose levels in acromegalic patients during administration of these compounds is thus mandatory.
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PMID:Pharmacologic therapies for acromegaly: a review of their effects on glucose metabolism and insulin resistance. 1564

Type 2 diabetes is associated with insulin resistance and reduced insulin secretion, which results in hyperglycaemia. This can then lead to diabetic complications such as retinopathy, neuropathy, nephropathy and cardiovascular disease. Although insulin resistance may be present earlier in the progression of the disease, it is now generally accepted that it is the deterioration in insulin-secretory function that leads to hyperglycaemia. This reduction in insulin secretion in Type 2 diabetes is due to both islet beta-cell dysfunction and death. Therefore, interventions that maintain the normal function and protect the pancreatic islet beta-cells from death are crucial in the treatment of Type 2 diabetes so that plasma glucose levels may be maintained within the normal range. Recently, a number of compounds have been shown to protect beta-cells from failure. This review examines the evidence that the existing therapies for Type 2 diabetes that were developed to lower plasma glucose (metformin) or improve insulin sensitivity (thiazolidinediones) may also have islet-protective function. Newer emerging therapeutic agents that are designed to increase the levels of glucagon-like peptide-1 not only stimulate insulin secretion but also appear to increase islet beta-cell mass. Evidence will also be presented that the future of drug therapy designed to prevent beta-cell failure should target the formation of advanced glycation end products and alleviate oxidative and endoplasmic reticulum stress.
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PMID:Investigational agents that protect pancreatic islet beta-cells from failure. 1618 66

There is a persistent perception that oestrogens have an adverse effect on carbohydrate metabolism. It might therefore be expected that their use would result in a corresponding increase in the incidence of diabetes. Recent evidence from clinical trials suggesting that women on postmenopausal oestrogen hormone replacement therapy (HRT) have a reduced incidence of type 2 diabetes therefore appears paradoxical. Short-term supraphysiological oestrogen administration has an adverse effect on glucose tolerance, resulting from suppression of first-phase insulin secretion and increased insulin resistance. Oestrogen-induced increases in glucocorticoid activity could account for these effects. Oestrogen-induced deterioration in glucose tolerance is, however, accompanied by a reduction in fasting glucose, an effect that could be accounted for by glucagon antagonism. These short-term effects contrast with long-term preservation of insulin secretion and glucose homeostasis by oestrogens. In animal studies, ovariectomy is associated with decreased insulin secretion and increased risk of diabetes, whereas oestrogen administration protects against diabetes and increases the insulin response to glucose. The mechanism is uncertain, but direct effects on the pancreas via steroid receptors or indirect effects via oestrogen-induced glucagon antagonism and subclinical increases in glucocorticoids and growth hormone could all contribute. Recent evidence that HRT increases the risk of cardiovascular disease suggests that it should not be used for the prevention of diabetes, but the mechanism responsible for this benefit merits further investigation and might lead to new therapies.
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PMID:Oestrogens and insulin secretion. 1619 92

Plant proteins have a reduced content of essential amino acids in comparison to animal proteins. A significant reduction of limiting amino acids (methionine, lysine, tryptophan) means lower protein synthesis. In subjects with predominant or exclusive consumption of plant food a higher incidence of hypoproteinemia due to significant reduction of methionine and lysine intakes was observed. On the other hand, lower intake of these amino acids provides a preventive effect against cardiovascular disease via cholesterol regulation by an inhibited hepatic phospholipid metabolism. Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine. When plant protein is high in non-essential amino acids, down-regulation of insulin and up-regulation of glucagon is a logical consequence. The action of glucagon in the liver is mediated by stimulation of adenyl cyclase that raises cyclic-AMP (adenosine-3,5-monophosphate) concentrations. Cyclic-AMP down-regulates the synthesis of a number of enzymes required for de novo lipogenesis and cholesterol synthesis, up-regulates key gluconeogenic enzymes and the LDL receptors and decreases the IGF-1 activity (insulin-like growth factor). Cyclic-AMP thus provides a reduction of atherosclerosis risk factors as well as a retardation of cancer development. A sufficient consumption of plant proteins has the protective effects against chronic degenerative diseases (Tab. 2, Ref. 26).
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PMID:Health benefits and risks of plant proteins. 1620 43

Dietary restriction of calories (caloric restriction [CR]) increases longevity in phylogenetically diverse species. CR retards or prevents age-dependent deterioration of tissues and an array of spontaneous and chemically induced diseases associated with obesity including cardiovascular disease, diabetes, and cancer. An understanding of the molecular mechanisms that underlie the beneficial effects of CR will help identify novel dietary, pharmacological, and lifestyle strategies for slowing the rate of aging and preventing these diseases as well as identify factors which modulate chemical toxicity. Here, we review the involvement of transcriptional coactivator proteins, peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 (PGC-1) alpha and beta, and regulated nuclear receptors (NR) in mediating the phenotypic changes found in models of longevity which include rodent CR models and mouse mutants in which insulin and/or insulin-like growth factor-I signaling is attenuated. PGC-1alpha is transcriptionally or posttranslationally regulated in mammals by: 1) forkhead box "other" (FoxO) transcription factors through an insulin/insulin-like growth factor-I -dependent pathway, 2) glucagon-stimulated cellular AMP (cAMP) response element binding protein, 3) stress-activated kinase signaling through p38 mitogen-activated protein kinase, and 4) the deacetylase and longevity factor sirtuin 1 (SIRT1). PGC-1alpha and PGC-1beta regulate the ligand-dependent and -independent activation of a large number of NR including PPARalpha and constitutive activated receptor (CAR). These NR regulate genes involved in nutrient and xenobiotic transport and metabolism as well as resistance to stress. CR reverses age-dependent decreases in PGC-1alpha, PPARalpha, and regulated genes. Strategies that target one or multiple PGC-1-regulated NR could be used to mimic the beneficial health effects found in models of longevity.
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PMID:Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity. 1642 81

Soybeans have a high-quality protein that has been consumed for approximately 5000 years in Oriental countries. The awareness that soy products are healthy has increased their consumption in Western countries. Substantial data from epidemiological surveys and nutritional interventions in humans and animals indicate that soy protein reduces serum total and low-density lipoprotein (LDL) cholesterol and triglycerides as well as hepatic cholesterol and triglycerides. This review examines the evidence on the possible mechanisms for which soy protein has beneficial effects in diabetes, obesity and some forms of chronic renal disease. Consumption of soy protein due to low methionine content reduces serum homocysteine concentration, decreasing the risk of acquiring a cardiovascular disease. On the other hand, soy protein reduces the insulin/glucagon ratio, which in turn down-regulates the expression of the hepatic transcription factor sterol regulatory element binding protein (SREBP)-1. The reduction of this factor decreases the expression of several lipogenic enzymes, decreasing in this way serum and hepatic triglycerides as well as LDL cholesterol and very LDL triglycerides in diabetes and obesity, reducing lipotoxicity in the liver. Soy protein intake also reduces hepatic lipotoxicity by maintaining the number of functional adipocytes, preventing the transfer of fatty acids to extra adipose tissues. Furthermore, soy protein isoflavones stimulate the transcription factor SREBP-2, increasing serum cholesterol clearance. The reduction of serum cholesterol and triglyceride concentrations by soy protein intake produces beneficial effects in the kidney preventing the inflammatory response, increasing the renal flow by releasing endothelial nitric oxide (NO) synthase from the caveolae, facilitating the synthesis of NO. Thus, soy protein consumption may reduce the clinical and biochemical abnormalities in diseases mediated by lipid disorders.
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PMID:Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders. 1648 Nov 55

There is a growing worldwide epidemic of obesity. Obese people have a higher incidence of type 2 diabetes and cardiovascular disease, and hence present increasing social, financial and health burdens. Weight loss is always difficult to achieve through lifestyle changes alone, and currently licensed anti-obesity drug treatments, such as orlistat and sibutramine, if tolerated, only achieve modest weight loss. Therefore, there is a need to identify more potent pharmacological targets. In the last 10 years, discoveries of new hormones such as leptin and ghrelin, together with greater understanding of previously described hormones such as cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), have led to a rapid increase in our knowledge of the regulation of energy balance. Among the most important factors, controlling appetite and satiety are peptide hormones released from the gut. In this paper, we provide a full up-to-date overview of the current state of knowledge of this field, together with the potential of these peptides as drugs, or as other therapeutic targets, in the treatment of obesity. Finally, we propose an integrated model to describe the complex interplay of these hormones in the broader physiology of energy balance.
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PMID:Gut peptides and the regulation of appetite. 1662 73

Significant interactions exist between fatty acids and the endocrine system. Dietary fatty acids alter both hormone and neuropeptide concentrations and also their receptors. In addition, hormones affect the metabolism of fatty acids and the fatty acid composition of tissue lipids. The principal hormones involved in lipid metabolism are insulin, glucagon, catecholamines, cortisol and growth hormone. The concentrations of these hormones are altered in chronic degenerative conditions such as diabetes and cardiovascular disease, which in turn leads to alterations in tissue lipids. Lipogenesis and lipolysis, which modulate fatty acid concentrations in plasma and tissues, are under hormonal control. Neuropeptides are also involved in lipid metabolism in brain and other tissues. Polyunsaturated fatty acids are also precursors for eicosanoids including prostaglandins, leucotrienes, and thromboxanes, which have hormone-like activities. Fatty acids in turn affect the endocrine system. Saturated and trans fatty acids decrease insulin concentration leading to insulin resistance. In contrast, polyunsaturated fatty acids increase plasma insulin concentration and decrease insulin resistance. In humans, omega3 polyunsaturated fatty acids alter the levels of opioid peptides in plasma. Free fatty acids have been reported to inhibit glucagon release. Fatty acids also affect receptors for hormones and neuropeptides.
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PMID:Relationship between fatty acids and the endocrine and neuroendocrine system. 1691 Jan 64


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