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

Research on antihypertensive drugs not only provides new information on presently used agents but also leads to the introduction of exciting new compounds. Several important clinical trials involving currently available drugs have been published recently. Angiotensin-converting enzyme inhibitors improved survival in patients with milder degrees of congestive heart failure, which indicates that they have become the cornerstone of treatment for this condition. Angiotensin-converting enzyme inhibitors delayed or prevented the development of diabetic proteinuria (> 200 micrograms/min) in a placebo-controlled randomized trial. Further, enalapril was more effective than metoprolol in reducing the rate of decline in renal function in patients with type I diabetes. Calcium channel blockers protected against acute renal failure in patients after renal transplantation in two separate studies. Calcium channel blockers were shown to promote natriuresis, with negative sodium balance the same as that associated with thiazide diuretics. The voltage-dependent calcium channel has been cloned, and the binding sites of the three classes of calcium channel blockers are now known. beta-Blockers and thiazide diuretics were the drug treatments in the Systolic Hypertension in the Elderly Program trial and in the Swedish Trial in Old Patients with Hypertension study (patients 65 to 85 years). In both investigations, stroke and cardiovascular events were significantly reduced by these conventional inexpensive agents. Clonidine was found to lower blood pressure primarily by its interaction with the imidazole receptor rather than the alpha 2 receptor. Elucidation of the imidazole receptor promises to shed light on physiologic mechanisms as well as lead to the introduction of new agents, such as moxonidine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New classes of antihypertensive drugs and new findings with established agents. 136 36

Diarrhea is a common gastrointestinal problem in diabetes, and its prevalence has been underestimated. The cause of diabetic diarrhea is unknown, but it is probably related to gastrointestinal motility disturbances secondary to diabetic autonomic neuropathy. Other causes (especially primary malabsorption syndromes and islet cell tumors) must be excluded. Treatment of diabetic diarrhea is largely symptomatic and only moderately effective. Antidiarrheal agents may ameliorate acute episodes. Broad-spectrum antibiotics and clonidine hydrochloride (Catapres) have had some success in long-term control. Most recently, subcutaneous administration of somatostatin analogues has been shown to be helpful, the main side effects being drowsiness and vomiting.
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PMID:Diabetic diarrhea. An underdiagnosed complication? 160 50

It has been suggested that the increased activity of the sympathetic nervous system and the resultant increase in the tissue catecholamine levels contribute to the pathogenesis of diabetes. In this study we evaluated the effect of clonidine, a central adrenergic agonist that decreases sympathetic tone, on the serum levels of glucose, insulin, glucagon and norepinephrine and on the hepatic glycogen content in normal and streptozotocin-diabetic rats. The animals were treated with clonidine 25 micrograms/kg/day interperitoneally for 3 weeks to suppress the central adrenergic impulses. Clonidine treatment significantly increased the weight gain, but did not affect plasma glucose, insulin, glucagon and norepinephrine in the diabetic animals. Pancreatic insulin and liver glycogen contents were significantly higher in the clonidine-treated than in the untreated diabetic rats. However, clonidine did not affect pancreatic insulin and liver glycogen content of nondiabetic animals. The intravenous administration of glucagon increased plasma glucose in the clonidine-treated, but not in the saline-treated diabetic rats. Insulin-induced hypoglycemia significantly enhanced glucagon release in clonidine-treated but not in saline-treated diabetic rats. We conclude that the suppression of central adrenergic activity may ameliorate the effects of insulin insufficiency on pancreatic hormone secretion and hepatic glycogen content.
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PMID:Central adrenergic suppression augments the insulin and glucagon secretory, and the glycogenolytic responses in streptozotocin-diabetic rats. 181 6

Adenylate cyclase activity was examined as a measure of inhibitory guanine nucleotide binding protein (Gi) function in liver plasma membranes from rats made chemically diabetic by streptozotocin (STZ) treatment. Clonidine activation of the alpha 2 adrenergic receptor, which activates Gi, inhibited forskolin--stimulated adenylate cyclase activity in control membranes. However, there was no effect on adenylate cyclase activity in membranes from STZ diabetic animals. Also, a polyclonal antipeptide antibody was raised to a highly conserved segment of the Gi alpha 2 subunit. This antibody specifically recognizes a 41 kilodalton protein, is blocked by an excess of peptide, does not recognize the alpha-subunit of transducin, and immunoprecipitates a 41 kilodalton protein which was ADP-ribosylated by pertussis toxin. Immunoblots using this antibody detect no difference between normal and STZ diabetic animals in the level of liver plasma membrane Gi expression. Therefore, STZ-induced diabetes altered the function of Gi but had no effect on Gi expression.
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PMID:The function but not the expression of rat liver inhibitory guanine nucleotide binding protein is altered in streptozotocin-induced diabetes. 190 25

Alterations in platelet function have been observed in a number of diabetic states. Increased responsiveness to platelet-aggregating agents in diabetes associated with increased catecholamine production and/or turnover suggested that heightened sympathetic activity may contribute to this increased platelet aggregation response. To investigate this possibility, we made male Wistar-Furth rats diabetic with streptozotocin and treated them either with adrenergic inhibitors (clonidine, yohimbine, reserpine) or saline. After 2 weeks, arterial blood samples were collected in 3.8% sodium citrate or acid citrate dextrose (ACD). Platelet-rich plasma (PRP) was prepared, and platelet aggregation studies were conducted directly or conducted on washed platelets prepared from PRP collected with ACD. Platelet aggregation in response to ADP by PRP was reduced while the rate of disaggregation was increased in platelets from diabetic animals when compared to controls. However, platelet aggregation in response to ADP in washed platelets was increased in diabetic animals when compared to controls. Clonidine, reserpine and yohimbine significantly decreased the diabetes-induced increase in maximum aggregation. Thrombin-induced aggregation was not altered by diabetes or any of the treatments. The platelet size was increased in the diabetic animals and was decreased toward controls by clonidine, reserpine and yohimbine treatment. These studies suggest that diabetes increases platelet aggregation response in diabetic rats, and that blockage or suppression of adrenergic activity reverses or attenuates the diabetes-induced hypersensitivity to ADP.
Diabetes Res Clin Pract 1990 Jul
PMID:Platelet aggregation and disaggregation in the streptozotocin induced diabetic rat: the effect of sympathetic inhibition. 214 2

The goal of this study was to confirm or rule out anecdotal reports of beneficial effects of clonidine and pentoxifylline in the treatment of painful diabetic peripheral neuropathy. Clonidine was administered to 16 subjects at two dosage levels (0.1 and 0.2 mg/day) and was compared to placebo in a crossover design, with each phase lasting 4 wk. Either pentoxifylline (400 mg 3 times/day) or placebo was given to 21 subjects in a 12-wk trial. Discomfort was characterized and rated with a subjective pain score (range 0-20). There was a significant decrease in pain score from baseline with both active drugs (P less than 0.05), but this was no better than the response to placebo (P less than 0.30 for clonidine and P less than 0.95 for pentoxifylline). This study does not demonstrate a short-term benefit of either clonidine or pentoxifylline in the treatment of peripheral neuropathy.
Diabetes Care 1990 Oct
PMID:Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. 181 83

To evaluate whether clonidine exerts its action within the central nervous system or outside the central nervous system to induce hyperglycemia, we compared the effects of clonidine injected into the third cerebral ventricle or intravenously on hepatic venous plasma glucose concentrations in fasted rats. Clonidine administration produced a dose-dependent hyperglycemia in each case. At all tested doses (5, 50, and 100 nmol) the hyperglycemic responses to clonidine injected intravenously were not significantly different from those to clonidine injected into the third cerebral ventricle. Intraperitoneal pretreatment with yohimbine (50 nmol) or phentolamine (50 nmol), both alpha-adrenergic antagonists, reduced the hyperglycemic response to clonidine (100 nmol) given intravenously, but these antagonists preinjected into the third cerebral ventricle did not reduce the response. Moreover, no significant differences in venous plasma clonidine concentrations were observed when intravenous and third cerebral ventricle injections of clonidine (100 nmol) were compared. These results suggest that clonidine-induced hyperglycemia is mainly mediated by the peripheral mechanism rather than through the central mechanism. To gain an insight into the peripheral mechanism for the hyperglycemic action of clonidine, we measured the plasma immunoreactive glucagon and insulin concentrations after intravenous clonidine (100 nmol). We found that plasma immunoreactive glucagon concentrations significantly increased, whereas plasma immunoreactive insulin concentrations did not change significantly despite hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Jan
PMID:Central versus peripheral effect of clonidine on hepatic venous plasma glucose concentrations in fasted rats. 289 76

The dynamics of growth hormone (GH) secretion in response to different GH secretagogues has been studied in adult freely moving male rats one month after induction of diabetes by single i.v. injection of streptozotocin (60 mg/kg). Baseline plasma GH concentrations and pituitary GH content were not different in streptozotocin-diabetic (St-D) rats and controls. Clonidine (0.15 mg/kg i.v.), an alpha 2-adrenergic agonist, failed to evoke GH release in St-D rats. Substitution therapy with insulin (1 IU/100 g b.wt.daily) delivered through subcutaneously implanted minipumps, allowed re-institution of a normal GH responsiveness to clonidine. At odds with clonidine, FK 33-824 (0.1 mg/kg i.v.), a potent analog of the opioid peptide Met-enkephalin, induced a similar rise in plasma GH levels in control and St-D rats. Finally, administration of a synthetic replicate of a GH-releasing hormone of human pancreatic origin, hpGRF-40 (2.5 micrograms/kg i.v.) elicited a higher GH response in St-D rats than in controls. These data indicate that in St-D rats: (1) an impaired function of noradrenergic pathways controlling GH release is present; (2) contrary to previous beliefs, an alpha 2-adrenergic mechanism is not involved in the GH-releasing effect of opioid peptides; and (3) pituitary GH responsiveness to hpGRF is increased.
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PMID:Effect of growth hormone-releasing stimuli in streptozotocin diabetic rats. 293 Nov 55

Elevated plasma growth hormone (GH) and peripheral catecholamine levels are frequently observed in poorly controlled, insulin-dependent diabetes. Since the alpha adrenergic system plays an important role in hypothalamic regulation of GH secretion, we tested the hypothesis that altered central adrenergic activity contributes to the increased GH concentrations in diabetes. Clonidine, an alpha-adrenergic agonist, was administered to nine poorly controlled, young diabetic patients (age 12-19 yr) before and after 1 wk of continuous subcutaneous insulin infusion pump therapy. As expected, continuous subcutaneous insulin infusion lowered mean 24-h plasma glucose (from 203 +/- 21 to 112 +/- 7 mg/dl, p less than 0.01) and GH (from 17.7 +/- 2.1 to 9.2 +/- 1.2 ng/ml, p less than 0.01) to values observed in normal controls. In the diabetic patients during conventional treatment, both the peak plasma GH level postclonidine (48.3 +/- 8.7 ng/ml) and the incremental area under the GH response curve (3.23 +/- 0.58 mg X min/ml) were significantly increased above normal control values (25.2 +/- 2.1 ng/ml, p less than 0.05 and 1.63 +/- 0.11 mg X min/ml, p less than 0.0025, respectively). In contrast, the GH response to clonidine was indistinguishable from normal after only 1 wk of intensified insulin treatment. Our findings support the contention that metabolic control of diabetes influences hypothalamic regulation of GH secretion and suggests that such alterations are related, at least in part, to changes in central alpha-adrenergic activity.
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PMID:Deranged alpha-adrenergic regulation of growth hormone secretion in poorly controlled diabetes: reversal of the exaggerated response to clonidine after continuous subcutaneous insulin infusion. 298 59

Glycosuria, hyperglycemia, and nephrotic-range proteinuria developed in a 68-year-old patient after clonidine was added to a stable antihypertensive regimen, which included metoprolol, of three years' duration. He later became glucose-intolerant with fasting hyperglycemia. Clonidine has been reported to transiently impair glucose tolerance. Persistent diabetes in a previously normoglycemic patient following clonidine has not been reported, and it supports the possibility that clonidine and metoprolol may have additive effects in suppressing endogenous insulin secretion.
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PMID:Nephrotic-range proteinuria and hyperglycemia associated with clonidine therapy. 351 63


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