TY - JOUR

T1 - Long-term exendin-4 treatment delays natural deterioration of glycaemic control in diabetic Goto-Kakizaki rats

AU - Simonsen, L

AU - Pilgaard, S

AU - Orskov, C

AU - Hartmann, B

AU - Holst, Jens Juul

AU - Deacon, C F

PY - 2009

Y1 - 2009

N2 - AIM: The glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4, has previously been shown to delay the onset of diabetes when administered to Goto-Kakizaki (GK) rats in the prediabetic period. The present study aimed to evaluate whether long-term administration of exendin-4 to GK rats in the diabetic period would improve their diabetes and how glycaemic control was affected following drug wash-out. METHODS: Glycaemic control was assessed in diabetic GK rats during 12 weeks of exendin-4 or vehicle treatment. Moreover, some animals were followed for an additional 9 weeks without treatment. RESULTS: Glycaemic control was seen to deteriorate in vehicle-treated animals, as assessed by increased glycated haemoglobin A1c (HbA1c), whereas HbA1c improved in exendin-4-treated animals. Following an additional 9 weeks without treatment, glycaemic control in exendin-4-treated animals remained below baseline value and thus remained significantly lower than that of vehicle-treated animals. Following exendin-4 administration, oral glucose tolerance tests revealed greatly reduced glucose and insulin excursions compared with vehicle-treated animals, whereas following overnight drug wash-out, only little difference was seen, suggesting that the improvement in glycaemic control may have been obtained primarily by increased postprandial control. No significant differences were observed in pancreatic islet morphology or islet hormone content. CONCLUSIONS: Exendin-4 treatment improved glycaemic control in diabetic GK rats, independent of changes in beta-cell mass. Additionally, progression of the disease seemed to be delayed because the improvement in HbA1c was still apparent 9 weeks after cessation of treatment.

AB - AIM: The glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4, has previously been shown to delay the onset of diabetes when administered to Goto-Kakizaki (GK) rats in the prediabetic period. The present study aimed to evaluate whether long-term administration of exendin-4 to GK rats in the diabetic period would improve their diabetes and how glycaemic control was affected following drug wash-out. METHODS: Glycaemic control was assessed in diabetic GK rats during 12 weeks of exendin-4 or vehicle treatment. Moreover, some animals were followed for an additional 9 weeks without treatment. RESULTS: Glycaemic control was seen to deteriorate in vehicle-treated animals, as assessed by increased glycated haemoglobin A1c (HbA1c), whereas HbA1c improved in exendin-4-treated animals. Following an additional 9 weeks without treatment, glycaemic control in exendin-4-treated animals remained below baseline value and thus remained significantly lower than that of vehicle-treated animals. Following exendin-4 administration, oral glucose tolerance tests revealed greatly reduced glucose and insulin excursions compared with vehicle-treated animals, whereas following overnight drug wash-out, only little difference was seen, suggesting that the improvement in glycaemic control may have been obtained primarily by increased postprandial control. No significant differences were observed in pancreatic islet morphology or islet hormone content. CONCLUSIONS: Exendin-4 treatment improved glycaemic control in diabetic GK rats, independent of changes in beta-cell mass. Additionally, progression of the disease seemed to be delayed because the improvement in HbA1c was still apparent 9 weeks after cessation of treatment.

U2 - 10.1111/j.1463-1326.2009.01066.x

DO - 10.1111/j.1463-1326.2009.01066.x

M3 - Journal article

C2 - 19508463

VL - 11

SP - 884

EP - 890

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 9

ER -