详细记录  
题名:Pioglitazone acutely reduces energy metabolism and insulin secretion in rats.
作者:LAMONTAGNE J; JALBERT-ARSENAULT E; PEPIN E; PEYOT ML; RUDERMAN NB; NOLAN CJ; JOLY E; MADIRAJU SR; POITOUT V; PRENTKI M;
来源:Diabetes. 2013 Jun;62(6):2122-9. doi: 10.2337/db12-0428. Epub 2013 Feb 1. [ IF= 8.29 ] ]
URL :10.2337/db12-0428
日期:20130702
摘要: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 beta-cell that may contribute to its capacity to lower insulinemia and
antidiabetic action.

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