Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM. However, some controversies still exist. In this report, the long-term effect of guar gum (Guarina) on both glycemic and blood lipid profiles was assessed in a randomized, double-blind and cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each subject received placebo (P) and Guarina (G) treatment for two eight-week periods separated by a four-week period to facilitate wash-out. Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired Student's t test). Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than 0.001). Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less than 0.005). Other variables, including serum total cholesterol, triglyceride, HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no significant changes during G or P treatment. Ten out of the 16 patients (62.5%) suffered from side effects; these included abdominal cramps (one case), diarrhea (seven cases) and skin itching (one case). In conclusion, guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM. Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject.
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PMID:Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus. 135 28

Ion channels in beta cells regulate electrical and secretory activity in response to metabolic, pharmacologic, or neural signals by controlling the permeability to K+ and Ca2+. The ATP-sensitive K+ channels act as a switch that responds to fuel secretagogues or sulfonylureas to initiate depolarization. This depolarization opens voltage-dependent calcium channels (VDCC) to increase the amplitude of free cytosolic Ca2+ levels ([Ca2+]i), which triggers exocytosis. Acetyl choline and vasopressin (VP) both potentiate the acute effects of glucose on insulin secretion by generating inositol 1,4,5-trisphosphate to release intracellular Ca2+; VP also potentiates sustained insulin secretion by effects on depolarization. In contrast, inhibitors of insulin secretion decrease [Ca2+]i by either hyperpolarizing the beta cell or by receptor-mediated, G-protein-coupled effects to decrease VDCC activity. Repolarization is initiated by voltage- and Ca(2+)-activated K+ channels. A human insulinoma voltage-dependent K+ channel cDNA was recently cloned and two types of alpha 1 subunits of the VDCC have been identified in insulin-secreting cell lines. Determining how ion channels regulate insulin secretion in normal and diabetic beta cells should provide pathophysiologic insight into the beta cell signal transduction defect characteristic of non-insulin dependent diabetes (NIDDM).
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PMID:The role of ion channels in insulin secretion. 138 42

Amylin, also called islet amyloid polypeptide (IAPP), or diabetes-associated peptide (DAP) is a recently discovered 37 amino acid polypeptide which has been shown to be co-secreted with insulin from the pancreatic beta-cell. The peptide turned out to be the major constituent of pancreatic amyloid deposits which are frequently found in the pancreas of type II diabetic patients. Therefore, a role for amylin in the aetiology of type II diabetes was hypothesized. To investigate this possibility, several studies have been performed to elucidate whether amylin is able to impair insulin secretion and action, two characteristic features of type II diabetes mellitus. These studies suggest that it is unlikely that amylin has a direct inhibitory effect on insulin secretion. Amyloid deposits, however, which are derived from the in situ polymerization and precipitation of amylin, may impair beta-cell function during type II diabetes by damaging and covering beta-cells. Furthermore, it has been shown that amylin has the potential to antagonize the action of insulin on glucose metabolism by increasing hepatic glucose production and by decreasing muscle, but not adipocyte glucose uptake. For these reasons, it has been suggested that amylin might be involved in the pathophysiology of type II diabetes and obesity, disease states which are characterized by abnormal beta-cell function and insulin resistance. In addition, amylin was shown to induce hypocalcaemia by inhibiting osteoclast-mediated bone resorption in a calcitonin-like manner. Therefore, amylin is likely to be involved in both the modulation of glucose and calcium metabolism.
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PMID:Biological action of pancreatic amylin: relationship with glucose metabolism, diabetes, obesity and calcium metabolism. 140 45

The entry of glucose into muscle cells is achieved primarily via a carrier-mediated system consisting of protein transport molecules. GLUT-1 transporter isoform is normally found in the sarcolemmal (SL) membrane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 transporters from an intracellular pool out to the T-tubule and SL membranes. Activation of transporters to increase the turnover number may also be involved, but the evidence is far from conclusive. When insulin binds to its receptor, it autophosphorylates tyrosine and serine residues on the beta-subunit of the receptor. The tyrosine residues are thought to activate tyrosine kinases, which in turn phosphorylate/activate as yet unknown second messengers. Insulin receptor antibodies, however, have been reported to increase glucose transport without increasing kinase activity. Insulin resistance in skeletal muscle is a major characteristic of obesity and diabetes mellitus, especially NIDDM. A decrease in the number of insulin receptors and the ability of insulin to activate receptor tyrosine kinase has been documented in muscle from NIDDM patients. Most studies report no change in the intracellular pool of GLUT-4 transporters available for translocation to the SL. Both the quality and quantity of food consumed can regulate insulin sensitivity. A high-fat, refined sugar diet, similar to the typical U.S. diet, causes insulin resistance when compared with a low-fat, complex-carbohydrate diet. On the other hand, exercise increases insulin sensitivity. After an acute bout of exercise, glucose transport in muscle increases to the same level as with maximum insulin stimulation. Although the number of GLUT-4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved. After an initial acute phase, which may involve calcium as the activator, a secondary phase of increased insulin sensitivity can last for up to a day after exercise. The mechanism responsible for the increased insulin sensitivity with exercise is unknown. Regular exercise training also increases insulin sensitivity, which can be documented several days after the final bout of exercise, and again the mechanism is unknown. An increase in the muscle content of GLUT-4 transporters with training has recently been reported. Even though significant progress has been made in the past few years in understanding glucose transport in skeletal muscle, the mechanisms involved in regulating transport are far from being understood.
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PMID:Regulation of glucose transport in skeletal muscle. 142 62

The authors summarize the principles of the therapeutic approach to the 5H syndrome [1. hyperinsulinism, 2. hyperglycaemia (NIDDM), 3. hyperlipoproteinaemia (obesity), 4. hypertension, 5. hirsutism], in particular its two components, i.e. NIDDM and arterial hypertension. The authors found that early treatment of hyperinsulinism, e.g. already in the stage of impaired glucose tolerance or NIDDM with oral antidiabetics, their disproportionate increase with regard to the blood sugar level and glycosylated haemoglobin without making "hygienic" provisions (radical weight reduction; increased physical activity to the maximum possible individual level; energy restricted diet in particular as regards carbohydrates and fat) does not prevent progression of the components of the 5H syndrome to the clinical stage. In treatment of arterial hypertension associated with 5H syndrome non-selective beta-blockers and thiazide diuretics are unsuitable because they worsen the HPLP and enhance insulin resistance. Suitable preparations are combinations of ACE-inhibitors, calcium antagonists, selective beta-blockers in particular with ISA and beta-blockers with a partial selective sympathomimetic activity (devalol and celiprolol). Hygienic provisions must be started in childhood, or when hyperinsulinism is detected.
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PMID:[How should we implement the basic principles of treatment of type 2 diabetes mellitus from the aspect of the hormono-metabolic syndrome X (5H)?]. 145 53

The clinical linkage of hypertensive cardiovascular disease, left ventricular hypertrophy, and accelerated atherosclerosis with a spectrum of metabolic disturbances including peripheral insulin resistance, hyperinsulinemia, obesity, and frank non-insulin dependent diabetes mellitus, has been increasingly appreciated. However, the underlying biologic basis mediating this clinical association remains unclear. Nuclear magnetic resonance techniques have been used to measure various intracellular ion species in human erythrocytes and have found that common, shared intracellular abnormalities of cytosolic free calcium, free magnesium, and pH occur in each of these clinical syndromes. Specifically, essential hypertension is characterized by higher fasting free cytosolic calcium concentrations and reciprocally lower intracellular free magnesium and pH levels compared with those of normotensive control subjects. Furthermore, for all subjects, free calcium and free magnesium levels were closely related both to the left ventricular mass and to the degree of insulin resistance present. Moreover, these same intracellular ionic lesions were found in normotensive obese and/or non-insulin diabetic individuals. Last, evidence has recently been provided that the cardiovascular consequences of increased dietary sugar and salt intake may well be determined by their concurrent influence on cellular ion metabolism. These data led to a hypothesis for a central role for altered cellular ion homeostasis in mediating the clinical linkage of cardiovascular and metabolic disease. According to this ionic hypothesis, essential hypertension, non-insulin dependent diabetes, and their frequently associated features of obesity, left ventricular hypertrophy, and accelerated atherosclerosis all derive from and reflect different clinical manifestations of the same underlying cellular lesion, characterized at least in part by elevated cytosolic free calcium and suppressed free magnesium levels.
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PMID:Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme. 145 64

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.
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PMID:Nicardipine does not cause deterioration of glucose homoeostasis in man: a placebo controlled study in elderly hypertensives with and without diabetes mellitus. 150 7

Amyloid deposits characteristically associated with pancreatic islets of those species (e.g., humans, cats, and monkeys) that develop age-associated forms of diabetes have been shown to represent a concentrated and polymerized form of a previously unknown islet-derived protein identified either as IAPP or amylin. IAPP, a highly conserved and carboxy-terminally amidated 37 amino acid polypeptide with approximately 45% amino acid sequence identity to CGRP, is produced by islet beta cells and is cosecreted with insulin in response to glucose and other secretagogues. Prepro-IAPP is synthesized in beta cells as an 89 to 93 amino acid molecule, and mature IAPP appears to be formed by enzymatic processing similar to that involved in the formation of insulin. Glucose-stimulated IAPP secretion generally parallels that of insulin and, on a molar basis, IAPP represents about 1% of the amount of insulin secreted. A significant dissociation of IAPP and insulin secretion (associated with relatively greater upregulation of IAPP secretion) is observed in response to marked hyperglycemia, suggesting that IAPP and insulin expression are differentially regulated. The amyloidogenicity of IAPP in only a very limited number of species is importantly related to the amino acid residues inherently found in the 20-29 region of IAPP from those species. The 25-28 region of human and cat IAPP is identical in structure and appears to be the most important amyloidogenic sequence common to the human and cat. In vitro fibrillogenesis studies have shown that amino acid substitutions in this region especially affect the amyloidogenicity of IAPP. Studies in dogs and cats suggest that aberrations in beta cell synthesis (or processing) of IAPP may lead to an increased concentration of IAPP in the local milieu, thus providing a second prerequisite for the self aggregation of IAPP to form islet amyloid. IAPP has been implicated to have physiological roles in glucose regulation, hemodynamics, calcium homeostasis, and as an anorectic agent. The major current interest in IAPP concerns its potential relationships to glucose metabolism and the development of type 2 diabetes. Evidence has been provided which indicates that IAPP can inhibit glucose-stimulated insulin secretion by beta cells, and that IAPP can also potentially contribute to the pathogenesis of type 2 diabetes by increasing hepatic glucose output and by inducing peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Islet amyloid polypeptide: mechanisms of amyloidogenesis in the pancreatic islets and potential roles in diabetes mellitus. 157 49

Renal protection is defined as an attenuation or significant slowing of the irrevocable decrease in renal function over time, which occurs subsequent to renal dysfunction. Control of systemic hypertension by whatever means exerts a renal protective effect. Evidence suggesting a specific action of individual antihypertensive agents is less certain. Calcium antagonists may exert a specific renal protective effect. Experiments in rats with reduced renal mass, desoxycorticosterone-induced hypertension, chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view. In three crossover trials, calcium antagonists reduced proteinuria in patients with type 2 diabetes mellitus. Preliminary data from a single prospective trial in patients with renal insufficiency offer additional support; however, definitive conclusions cannot be reached without further trials. In particular, comparative trials of different classes of antihypertensive agents with equal blood pressure control are needed. Thus far, only reducing systemic blood pressure per se has been shown to be of value in attenuating hypertension-induced renal dysfunction in humans.
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PMID:Are calcium antagonists of value in ameliorating the course of chronic renal disease? 161 61


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