title: Pioglitazone acutely reduces energy metabolism and insulin secretion in rats.
abstract: Our objective was to determine if the insulin-sensitizing drug pioglitazone acutely reduces insulin secretion and causes metabolic deceleration in vivo independently of change in insulin sensitivity. We assessed glucose homeostasis by hyperinsulinemic-euglycemic and hyperglycemic clamp studies and energy expenditure by indirect calorimetry and biotelemetry in male Wistar and obese hyperinsulinemic Zucker diabetic fatty (ZDF) rats 45 min after a single oral dose of pioglitazone (30 mg/kg). In vivo insulin secretion during clamped hyperglycemia was reduced in both Wistar and ZDF rats after pioglitazone administration. Insulin clearance was slightly increased in Wistar but not in ZDF rats. Insulin sensitivity in Wistar rats assessed by the hyperinsulinemic-euglycemic clamp was minimally affected by pioglitazone at this early time point. Pioglitazone also reduced energy expenditure in Wistar rats without altering respiratory exchange ratio or core body temperature. Glucose-induced insulin secretion (GIIS) and oxygen consumption were reduced by pioglitazone in isolated islets and INS832/13 cells. In conclusion, pioglitazone acutely induces whole-body metabolic slowing down and reduces GIIS, the latter being largely independent of the insulin-sensitizing action of the drug. The results suggest that pioglitazone has direct metabolic deceleration effects on the β-cell that may contribute to its capacity to lower insulinemia and antidiabetic action.
authors: Molecular Nutrition Unit and Montreal Diabetes Research Center at the Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.
authors: Julien
authors: J
authors: Lamontagne
authors: Elise
authors: E
authors: Jalbert-Arsenault
authors: Emilie
authors: E
authors: Pepin
authors: Marie-Line
authors: ML
authors: Peyot
authors: Neil B
authors: NB
authors: Ruderman
authors: Christopher J
authors: CJ
authors: Nolan
authors: Erik
authors: E
authors: Joly
authors: S R Murthy
authors: SR
authors: Madiraju
authors: Vincent
authors: V
authors: Poitout
authors: Marc
authors: M
authors: Prentki
mesh_terms: D000818:Animals; D002153:Calorimetry, Indirect; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone
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