1. Beta-cell insulin secretory response to oral hypoglycemic agents is blunted in humans in vivo during moderate hypoglycemia
- Author
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Clara Bouche, Jen Armstrong, Alan C. Moses, Allison B. Goldfine, Richard D. Carr, and Waleed Aldhahi
- Subjects
Counterregulatory hormone ,Adult ,Male ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Administration, Oral ,Hypoglycemia ,Biochemistry ,chemistry.chemical_compound ,Islets of Langerhans ,Endocrinology ,Double-Blind Method ,Piperidines ,Diabetes mellitus ,Internal medicine ,Insulin Secretion ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Pancreatic hormone ,Cross-Over Studies ,C-peptide ,business.industry ,Biochemistry (medical) ,nutritional and metabolic diseases ,medicine.disease ,Repaglinide ,Glucose ,chemistry ,Female ,Carbamates ,business ,Glipizide ,medicine.drug - Abstract
Oral hypoglycemic agents bind to the ATP-sensitive potassium channel and lower glucose levels effectively in individuals with diabetes. Although the principle mechanism of action can also promote hypoglycemia, clinically profound hypoglycemia is rare. Decreased stimulation of insulin secretion by these agents at mild hypoglycemia could provide protection from more profound hypoglycemia. Sulfonylureas and meglitinides bind to both shared and unique sites on the ATP-sensitive potassium receptor/channel complex but have different pharmacokinetic profiles. To evaluate the differential ability of both sulfonylureas and meglitinides to stimulate insulin release at modest hypoglycemia, we evaluated dextrose infusion rates necessary to maintain plasma glucose after oral administration of repaglinide (1 mg) or glipizide (5 mg) at euglycemia and again at modest hypoglycemia. Healthy subjects with no family history of diabetes underwent four clamp studies, two performed while maintaining isoglycemia (glucose levels at the fasted value) and two while maintaining modest hypoglycemia of 2.78 mmol/liter (50 mg/dl) induced by low-dose insulin infusion (3.6 pmol/kg.min). There was a marked decrease in the dextrose infusion rate with administration of either repaglinide or glipizide at hypoglycemia compared with drug administration at euglycemia (P
- Published
- 2004