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)

The addition of phenobarbital (PB) to a sulphonylurea (SU) regimen may improve glycemic control in patients with non- insulin dependent diabetes mellitus (NIDDM, type II). Since SU reactions may be modified, we investigated glucose metabolism in rats with combined PB and SU treatment. Chlorpropamide (CHL) and glibenclamide (GB) were selected as SU drugs. The combination of PB to the CHL or GB regimens induced the drug metabolism enzymes excluding aminopyrine N-demethylase activity, which was enhanced by GB but not CHL. The CHL and GB treatments lowered blood glucose (BG) concentration and decreased hepatic glucose-6-phosphate phosphohydrolase (G6P hydrolase) activity and glycogen reserves in the rats. The concomitant administration of PB and the SUs decreased hepatic G6P hydrolase activity and glycogen content in the animals, whereas the BG level remained unaltered. The hepatic glycogen content was decreased more markedly in the CHL plus PB than in the CHL alone treated animals. The findings suggests that enzyme inducers modify the action of SU in rats. Hepatic drug and glucose metabolizing enzymes seems also to respond to distinct PB plus SU combinations in different ways.
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PMID:Sulphonylureas and glucose metabolism in phenobarbital induced rats. 378 43

Indirect evidence suggests that sulfonylureas, in addition to stimulating insulin release, exert additional effects at extrapancreatic levels which are of value in the management of type 2 diabetes. In order to characterize in vivo some of these effects, insulin sensitivity was studied in 9 type 1 diabetics with no residual insulin secretory activity, during treatment with chlorpropamide (250 mg b.i.d. for 8 days) and with glipizide (5 mg t.i.d. for 8 days). Employing the glucose clamp technique with the aid of an artificial pancreas (Biostator), glucose disposal during insulin infusion (0.1 U/kg in 60 min) was calculated by the amount of glucose required to keep the blood glucose at preinfusion levels. Chlorpropamide and glipizide administration was accompanied by a significant increase of the amount of glucose required to clamp blood glucose levels, while serum (free) insulin levels were superimposable during the different clamping studies. In the absence of endogenous insulin release, these data strongly suggest that the two sulfonylureas employed enhance in vivo the peripheral sensitivity to insulin. Further studies are required to indicate a preferential site of action (liver, muscle, adipose tissue) of sulfonylureas.
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PMID:Sulfonylureas enhance in vivo the effectiveness of insulin in type 1 (insulin dependent) diabetes mellitus. 639 58

Chlorpropamide-alcohol flushing (CPAF) has been advanced and challenged as a specific marker for familial noninsulin dependent diabetes mellitus. The previous studies assay flushing reactions employing arbitrarily defined critical threshold values of rise and rate of rise in facial temperature. Since these methods ignore the curvilinear relationship between skin temperature and cutaneous blood flow, errors of analysis obtained, Further, the role of baseline facial temperature is obfuscated. The method of malar thermal circulation index derived from the relationship between skin temperature and cutaneous blood flow provides a more accurate assay method and permits the characterization of the role of baseline facial temperature. Baseline facial temperature is less in subjects with CPAF and noninsulin dependent diabetes than in normal subjects. The lower baseline facial temperature alone may account for the reported differences in the parameters of the CPAF test.
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PMID:Chlorpropamide-alcohol flushing, malar thermal circulation index, and baseline malar temperature. 712 Dec 66

Chlorpropamide (CP), a sulfonylurea used for treatment of non-insulin dependent diabetes mellitus, is known to potentiate the antidiuretic action of arginine vasopressin (AVP), predisposing to hyponatremia. It has been suggested that CP acts directly on the antidiuretic vasopressin receptor. Detailed studies on the influence of CP on the AVP receptor, however, have been hampered by lack of a suitable radioligand. Using a newly developed radioiodinated derivative of AVP with high specific activity and high affinity for the AVP V2-receptor (125I-[8-(p-(OH)-phenylpropionyl)]-LVP), we studied the role of AVP V2-receptors in CP-induced water retention. Male-Sprague-Dawley rats were treated orally with 40 mg CP/day or placebo for 7 days, after which Scatchard analysis was performed using membranes prepared from homogenized renal papilla. After oral water load, CP-treated rats but not control rats showed a significant decrease in plasma osmolality (289 +/- 2.2 to 284 +/- 0.8 mosmol/kg, p < 0.05). The Kd was 0.69 +/- 0.16 nmol/l in controls and 0.70 +/- 0.12 nmol/l after CP treatment (NS); Bmax was 129 +/- 5.3 nmol/kg protein in controls (N = 8). Chlorpropamide significantly increased receptor density (Bmax) to 167 +/- 8.4 nmol/kg protein (N = 8) (p < 0.05). Plasma AVP did not change significantly during CP treatment. These data show for the first time that CP in vivo increases the density of AVP V2 receptors without altering plasma AVP. This is associated with an impairment in water excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors. 771 84

The leaf of Psidium guajava Linn. (family, Myrtaceae) is used traditionally in African folk medicine to manage, control, and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the anecdotal, folkloric, ethnomedical uses of P. guajava Linn., the present study was undertaken to investigate the hypoglycemic and hypotensive effects of P. guajava leaf aqueous extract (PGE, 50-800 mg/kg) in rat experimental paradigms. The hypoglycemic effect of the plant's extract was examined in normal and diabetic rats, using streptozotocin (STZ)-induced diabetes mellitus model. Hypertensive Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant's extract. Chlorpropamide (CPP; 250 mg/kg, p.o.) was used as the reference hypoglycemic agent for comparison. Acute oral administrations of the plant's extract (PGE; 50-800 mg/kg, p.o.) caused dose-related, significant (p < 0.05-0.001) hypoglycemia in normal (normoglycemic) and STZ-treated, diabetic rats. Moreover, acute intravenous administrations of the plant's extract (PGE, 50-800 mg/kg i.v.) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressures and heart rates of hypertensive, Dahl salt-sensitive rats. Although the exact mechanisms of action of the plant's extract still remain speculative at present, it is unlikely that the extract causes hypotension in the mammalian experimental animal model used via cholinergic mechanisms, since its cardiodepressant effects are resistant to atropine pretreatment. The numerous tannins, polyphenolic compounds, flavonoids, pentacyclic triterpenoids, guiajaverin, quercetin, and other chemical compounds present in the plant are speculated to account for the observed hypoglycemic and hypotensive effects of the plant's leaf extract. However, the results of this experimental animal study indicate that the leaf aqueous extract of P. guajava possesses hypoglycemic and hypotensive properties, and thus lend pharmacological credence to the suggested folkloric, ethnomedical uses of the plant in the management or control of adult-onset, type 2 diabetes mellitus and hypertension in some rural African communities.
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PMID:Hypoglycemic and hypotensive effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract. 1639 18

The stem bark of Harpephyllum caffrum Bernh ex CF Krauss (family: Anacardiaceae) is used traditionally in African folk medicine to manage, control and/or treat an array of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the anecdotal, folkloric and ethnomedical uses of Harpephyllum caffrum, this study was undertaken to examine the hypoglycaemic and hypotensive effects of Harpephyllum caffrum stem bark aqueous extract (HCE) in rat experimental paradigms. The hypoglycaemic effect of the plant extract (HCE) was examined in normal and diabetic rats, using a streptozotocin (STZ)-induced diabetes mellitus model. Hypertensive, Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant extract. Chlorpropamide (250 mg/kg po) was used as the reference hypoglycaemic agent for comparison. Acute oral administrations of the plant extract (HCE, 50-800 mg/kg po) caused dose-related, significant (p < 0.05- 0.001) hypoglycaemia in normal (normoglycaemic) and STZ-treated diabetic rats. Furthermore, acute intravenous administrations of the plant extract (HCE, 25-400 mg/kg iv) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressures and heart rates of the hypertensive, Dahl salt-sensitive rats used. Although the exact mechanisms of action of the plant extract still remain obscure at the moment, it is unlikely that the plant causes hypotension in the mammalian experimental animal model used, via the cholinergic mechanism, since its hypotensive effect was resistant to atropine pretreatment. The numerous polyphenolic compounds and flavonoids present in the plant are speculated to account for the observed hypoglycaemic and hypotensive effects of the extract. However, the findings of this experimental animal study indicate that the stem-bark aqueous extract of H caffrum possesses hypoglycaemic and hypotensive properties, and thus lend pharmacological support to the suggested folkloric, anecdotal and ethnomedical uses of the plant in the management and/or control of adult-onset type 2 diabetes mellitus and hypertension in some rural communities of southern African.
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PMID:Hypoglycaemic and hypotensive effects of Harpephyllum caffrum Bernh ex CF Krauss (Anacardiaceae) stem-bark aqueous extract in rats. 1673 99