BACKGROUND: Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes.
OBJECTIVE: We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines.
DESIGN AND METHODS: After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG), the oral glucose tolerance test (OGTT, insulinogenic index) and the graded-hyperglycemic clamp (clamp insulinogenic index). Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro.
RESULTS: OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5%) (P = 0.011). IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9%) (P = 0.002). AIRG decreased by 54.0% (IQR, 40.7%) (P = 0.010), leading to mild fasting hyperglycemia (P = 0.039). Exenatide, compared with placebo, decreased body weight (P
CONCLUSIONS: In pre-diabetic canines, 12-week exenatide treatment improved β-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes.
Ionut, Viorica; Woolcott, Orison O; Mkrtchyan, Hasmik J; Stefanovski, Darko; Kabir, Morvarid; Iyer, Malini S; Liu, Huiwen; Castro, Ana V B; Wu, Qiang; Broussard, Josiane L; Kolka, Cathryn M; Asare-Bediako, Isaac; and Bergman, Richard N, "Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes." (2016). Integrative Physiology Faculty Contributions. 8.