Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective population study of women in Gothenburg, Sweden, showed an increased risk of developing diabetes in women taking diuretics or beta-blockers as antihypertensive agents compared to other women. The risk seemed to be still higher, if the combination of diuretics and beta-blockers was used. The same observation was made also when the study was confined to hypertensive women indicating that not only the hypertensive state but also the antihypertensive drugs per se may be a risk factor for developing diabetes. This possibility is further strengthened by the fact that, as far as diabetes type II is concerned, the hypertensive state in most cases precedes the development of diabetes, while only few subjects with diabetes type II develop arterial hypertension. We could only study the possible diabetic effect of diuretics and beta-blockers. It must, however, be of great interest to study alpha-blockers, calcium antagonists and ACE inhibitors in the same way. If one or more of these new substances will prove not to be diabetogenic, this will be a very important factor in our choice of first drug in the treatment of arterial hypertension.
 ...
PMID:Incidence of diabetes during antihypertensive treatment. 197 45

Overweight and obesity may develop in individuals with genetically determined low resting energy expenditure. Drugs are among the recognised precipitating factors. The obesity promoting impact of beta-blockers is, however, less well known. Resting energy expenditure, and thermogenesis induced by stimuli such as meals, cold and heat exposure, stress and anxiety, have a facultative component mediated by the sympathoadrenal system through catecholamines working on beta-adrenoceptors. Treatment with beta-blockers reduces the facultative thermogenesis by 50-100 kcal/d, which corresponds to the weight gain of 2-5 kg/year reported in clinical trials. Treatment with beta-blockers also results in insulin resistance, which may aggravate existing diabetes and elicit diabetes in predisposed patients. Overweight and obesity are frequently complicated with hypertension and angina pectoris, which are often treated with beta-blockers. Obesity is associated with a defective sympathetic activity, and treatment with beta-blockers may further reduce facultative thermogenesis and promote weight gain. The consequence may be aggravation of hypertension, insulin resistance and other atherogenic factors. The causal therapy of android overweight and obesity complicated with diabetes or hypertension is a sufficient weight loss. If pharmacological treatment is inevitable, combined treatment with diuretics and ACE-inhibitors are most appropriate.
 ...
PMID:[Obesity and diabetes as side-effects of beta-blockers]. 197 28

Hypertension occurs in about 40% of patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom the incidence of coronary heart disease is greatly increased. Disturbances in lipid metabolism may be an important contributory factor. Patterns of lipid change in uncomplicated NIDDM are characterised by a raised serum triglyceride and a reduced high density lipoprotein. It is therefore likely that therapy for hypertension associated with NIDDM may further influence an existing atherogenic lipid profile. Recent studies in diabetic subjects have shown that alpha-blockers are associated with a trend towards improving, while beta-blockers adversely affect, the lipid profile. Calcium antagonists and ACE inhibitors have no adverse effects on the lipid profile.
 ...
PMID:Antihypertensive drugs and the hypertensive diabetic patient. 197 21

The pathophysiological connections between insulin resistance, hypertension and type 2 diabetes are discussed in this review article. Increased blood pressure levels are often found in type 2 diabetic patients long before the diabetes itself is diagnosed. By contrast, in type 1 diabetes hypertension is predominantly the consequence of diabetic glomerulopathy. Non-pharmacological strategies should be favoured in the treatment of hypertension in type 2 diabetic patients before specific pharmacological intervention is started. Antihypertensive treatment with beta-blocking agents and diuretics is criticized by many experts in the field of metabolic disorders, since these drugs induce a deterioration of glycaemic control and lipid metabolism in diabetic patients. Since calcium channel blockers, ACE inhibitors and alpha 1-specific blocking agents have no influence on metabolism, these drugs are recommended for the antihypertensive treatment of diabetic patients. Further studies should be undertaken to clarify, whether ACE-inhibitors have a specific nephroprotective effect. Since most type 2 diabetic patients do not develop diabetic nephropathy, a possible nephroprotective effect of ACE inhibitors is only relevant to the antihypertensive treatment of type 1 diabetic patients.
 ...
PMID:[Hypertension, insulin resistance and diabetes mellitus: pathophysiological interactions and therapeutic consequences]. 198 Jul 67

In two cases with drug-related hyperkalemia, potassium homeostasis, causes, symptoms and therapy are discussed. Iatrogenic and therefore avoidable hyperkalemia occurs most often when potassium, ACE-inhibitors, nonsteroidal antiinflammatory drugs or potassium-sparing diuretics are administered in patients with impaired renal function or diabetes mellitus. The emergency treatment in patients with severe hyperkalemia consists of intravenous calcium injections, infusion of glucose with insulin and, more recently, salbutamol. With acidotic patients administration of sodium-bicarbonate can be tried. Ion-exchange drugs and furosemide have a more delayed effect. With oliguria and anuria hemodialysis is often necessary.
 ...
PMID:[Hyperkalemia]. 199

Fluorometry and high-performance liquid chromatography were used to measure the content of free CoA and the esters of acetate, malonate, succinate, and long-chain fatty acids in isolated perifused rat pancreatic islets exposed to 25 mM glucose or a mixture of fuels (25 mM glucose plus 10 mM glutamine, 10 mM lactate, and 1 mM pyruvate) to assess the role of intermediates of lipid metabolism as candidate metabolic coupling factors in the mechanism of fuel-induced insulin secretion. Insulin secretion was stimulated in a biphasic manner with the fuel mixture, showing twice the potency compared with high glucose alone. Islets perifused for 3 min with high glucose alone or the fuel mixture compared with 2.5 mM glucose showed a significant increase in malonyl-CoA and succinyl-CoA and a decrease in acetyl-CoA. Free CoA and long-chain acyl-CoA levels were unaltered. Perifused islets stimulated with 25 mM glucose for 30 min showed a significant increase in succinyl-CoA and long-chain acyl-CoA and decrease in acetyl-CoA, whereas malonyl-CoA was not affected. However, when islets were stimulated by the fuel mixture for 30 min, malonyl-CoA was maintained at a high level, and the change in succinyl-CoA and long-chain acyl-CoA was similar to that observed in islets stimulated with 25 mM glucose alone. The acetyl-CoA concentration in the islets stimulated with the fuel mixture decreased slightly. These results confirm the viability of the hypothesis that malonyl-CoA and long-chain acyl-CoA serve as metabolic coupling factors in signal transduction when islets are stimulated by high glucose or glucose combined with other fuels.
Diabetes 1991 Mar
PMID:Content of CoA-esters in perifused rat islets stimulated by glucose and other fuels. 199 74

The metabolic changes which accompany hyperglycemia in a person with diabetes are thought to cause renal hyperperfusion and intraglomerular hypertension, especially in the person with a predisposition to essential hypertension. Intraglomerular hypertension causing deposition of protein in the mesangium leads to glomerulosclerosis and renal failure. Screening for microalbuminuria can predict which type I diabetic patients will develop nephropathy. The decline in renal function in established diabetic nephropathy can be slowed with aggressive treatment of hypertension. The use of ACE inhibitors may also decrease intraglomerular hypertension. Whether similar treatment in the person with preclinical diabetic nephropathy would delay or prevent the onset of diabetic nephropathy is being investigated. Restricted protein intake, anti-platelet and rheolitic drugs may have a role in the treatment of established diabetic nephropathy. In end stage renal failure, renal transplantation is the treatment of choice. When transplantation cannot be performed, chronic ambulatory peritoneal dialysis is preferable to hemodialysis.
 ...
PMID:Diabetic nephropathy: changing concepts of pathogenesis and treatment. 200 Aug 93

The effect of treatment with enalapril (10 days at 10 mg/d followed by 4 weeks at 20 mg/d) on forearm hemodynamics was assessed in eight normotensive patients and eight patients with hypertension affected by Type II diabetes as well as in eight patients with essential hypertension and normal glucose tolerance. The ACE inhibitor decreased regional vascular resistances and increased the maximum arteriolar-vasodilating capacity and venous distensibility in the three groups of patients. Thus, this study shows that ACE inhibition by enalapril improves regional hemodynamics in patients with Type II diabetes.
 ...
PMID:The effect of ace inhibition on peripheral hemodynamics in normotensive and hypertensive patients with type II diabetes. 201 May 59

Perifused islets from rats infused for 7 days with 40% glucose exhibited an altered secretory response to selected stimuli. Both phases of insulin release were blunted when 20 mM L-leucine was tested; the secretory response to a subsequent leucine stimulation was also blunted compared with the control group. The ability of 20 mM alpha-ketoisocaproate to stimulate the release of insulin was also greatly diminished in islets from glucose-infused rats. The secretory response to 50 microM tolbutamide plus 7 mM glucose by perifused islets from glucose-infused rats was 45% lower than in the control group. In addition, the response to a subsequent 10 mM glucose stimulation was lost. On the other hand, islets from glucose-infused rats responded to 20 microM forskolin plus 16.7 mM glucose with on significant change in the amount of insulin released during both phases of stimulation compared with the control group. The response to 100 nM phorbol 12-myristate 13-acetate was 3.1-fold higher in islets from glucose-infused compared with saline-infused rats. The finding that chronic infusions of glucose lead to selective impairment of the secretory response to fuel stimuli and agents such as tolbutamide that act on metabolically regulated K+ channels gives support to the notion that alterations in the generation of metabolic coupling signals might be involved in the phenomenon described here.
Diabetes 1991 Jan
PMID:Insulin secretory response to secretagogues by perifused islets from chronically glucose-infused rats. 201 70

The effect of activators of protein kinase C (PKC) on cytosolic concentration of free Ca2+ [( Ca2+]i) was assessed in insulin-secreting islet cell line HIT T-15. Dioctanoylglycerol (DiC8) and 12-O-tetradecanoylphorbol-13-acetate (TPA) evoked activation of PKC. Basal [Ca2+]i was 65-160 nM. DiC8 induced triphasic increases in [Ca2+]i; phase 2 was the most prominent and consistent one. With 25-150 microM DiC8, [Ca2+]i increased in a dose-dependent manner during phase 2; half-maximal stimulatory dose was 53 microM. TPA did not evoke any increase in [Ca2+]i. Staurosporine, sphingosine, and H7, which are inhibitors of PKC, did not block DiC8-induced rise in [Ca2+]i. DiC8-induced rise in [Ca2+]i was also seen in cells that had been depleted of PKC by prior exposure to TPA. DiC8-induced rise in [Ca2+]i still occurred in the presence of the Ca(2+)-channel blocker verapamil or when the extracellular Ca2+ had been reduced from 2.5 mM to 30 nM by EGTA. Three immediate metabolites of DiC8, monooctanoylglycerol, octanoate, and glycerol, did not evoke any change in [Ca2+]i. Monooleoylglycerol and R59022, which induce increases in endogenous diacylglycerol (DAG) by inhibiting DAG kinase, evoked increases in [Ca2+]i. DiC8 did not cause any change in inositol 1,4,5-trisphosphate levels. DiC8 evoked biphasic increases in insulin release; the second-phase increase in [Ca2+]i preceded the late phase of insulin secretion. Exogenous DAGs should be used with caution in assessing PKC function. Changes in the generation in DAGs must be included among the mechanisms by which Ca2+ homeostasis is regulated in islet cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 May
PMID:Dioctanoylglycerol regulation of cytosolic Ca2+ by protein kinase C-independent mechanism in HIT T-15 islet cells. 202 6


<< Previous 1 2 3 4 5 6 7 8 9 10