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Metabolism. 1991 Nov;40(11):1173-7.
Improvement of glucose-primed intravenous glucose tolerance and correction of acute insulin decrement by glipizide in type II diabetes.

Ravanam A, Jeffery J, Nehlawi M, Abraira C.

Endocrinology Section, Hines VA Hospital, IL 60141.

Improved glucose disposal after repeated intravenous (IV) glucose loads, known as the Staub effect, is absent in both type I and type II diabetes. Acute decrements of insulin secretion (AID) are observed following the early phase of insulin release on IV glucose stimulation in non-insulin-dependent diabetes mellitus (NIDDM). The AID cannot be corrected by acute infusions of glyburide or glipizide, or phentolamine, or by glycemic control after 2 weeks of intensive insulin treatments. Fifteen male subjects had 3 hourly successive IV glucose tolerance tests before and after 6 months of glipizide, at a final maintenance dose of 30 +/- 3 mg/d. Before treatment, AID, defined as the difference of the lowest of post IV glucose 7- or 10-minute samples from the preceding baseline insulin levels, was detected in the three loads: -6.4 +/- 1.9 microU/mL in the first, and then more consistently in the second and third loads, -11 +/- 2 microU/mL, and -17 +/- 9 microU/mL, respectively. There was a stepwise increase in insulin sums after each load. After glipizide therapy, the AIDS following all three IV glucose loads were no longer demonstrable; both insulin values, as well as insulin sums, were significantly elevated after all three glucose loads. While in the untreated state, the Staub effect was absent: serum glucose disappearances (K), corrected for glycosuria, were K1 = 0.52 +/- 0.02, K2 = 0.50 +/- 0.04, and K3 = 0.52 +/- 0.03.(ABSTRACT TRUNCATED AT 250 WORDS)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1943745&dopt=Abstract




Diabetes Res Clin Pract. 1991 Jan;11(1):47-52.
Direct effect of hypoglycemic sulphonylureas on the cardiovascular system of dogs.

Ballagi-Pordany G, Koltai MZ, Aranyi Z, Pogatsa G.

National Institute of Cardiology, Research Department, Budapest, Hungary.

The effects of first generation sulphonylurea compounds carbutamide, gliclazide and tolbutamide as well as second generation compounds glibenclamide and glipizide on the cardiovascular system were investigated in dogs. Six dogs received each compound intravenously at cumulative dose levels of 74, 296, 1184 mumol/kg of carbutamide and tolbutamide, 0.4, 2.0, 10.0 mumol/kg of glibenclamide and glipizide, and 16, 48 and 144 mumol/kg of gliclazide. Mean arterial blood pressure, myocardial contractile force, cardiac output and heart rate were measured. The rate of change of myocardial contractile force development (positive dF/dt), as well as of myocardial relaxation (negative dF/dt) were measured. The first generation sulphonylureas were found, in dogs, to exert a positive inotropic effect in contrast to second generation compounds. The clinical importance of our findings may be in the potential for the malfunction of the cardiovascular system (based on cardiopathy, neuropathy, atherosclerosis, and obesity), developing in diabetes, to be further impaired by the first generation sulphonylureas. Therefore, second generation sulphonylureas should be preferred in the therapy of type 2 diabetics, if satisfactory metabolic control cannot be achieved by dietary management alone and sulphonylurea treatment becomes necessary.

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Diabetes Res Clin Pract. 1990 Jan;8(2):109-14.
Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds.

Ballagi-Pordany G, Koszeghy A, Koltai MZ, Aranyi Z, Pogatsa G.

National Institute of Cardiology, Research Department, Budapest, Hungary.

The effects of first and second generation hypoglycemic sulfonylureas on the incidence of ventricular ectopic beats and on the duration of transitional ventricular fibrillation in the ischemic rat heart were investigated. First generation sulfonylurea compounds (tolbutamide, carbutamide and gliclazide) in 105 preparations increased, while second generation sulfonylurea compounds (glibenclamide and glipizide) in 50 preparations decreased in a dose-dependent manner both the number of ventricular ectopic beats and the duration of transitional ventricular fibrillation during the first 30 min after ligation of the left anterior descending coronary artery. Therefore, second generation sulfonylureas should be preferred in the treatment of type 2 diabetics with ischemic heart diseases, if satisfactory metabolic control cannot be achieved by a treatment regimen and diet alone.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2106423&dopt=Abstract













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