Abstract
Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia. Male Sprague-Dawley rats were given daily subcutaneous doses of Cd at 0.6 mg/kg over 12 weeks. There was a resulting time-dependent increase in fasting blood glucose and altered insulin release in vitro. Islets isolated from control (saline-treated) and Cd-treated animals were incubated in low (0.5 mg/mL) or high (3 mg/mL) glucose conditions. Islets from 12 week Cd-treated animals had significantly less glucose-stimulated insulin release compared to islets from saline-treated control animals. The actual Cd content of isolated islets was 5 fold higher than the whole pancreas (endocrine + exocrine) and roughly 70% of that present in the renal cortex. Interestingly, islets isolated from Cd-treated animals and incubated in high glucose conditions contained significantly less Cd and zinc than those incubated in low glucose. These results show that within whole pancreatic tissue, Cd selectively accumulates in pancreatic islets and causes altered islet function that likely contributes to dysglycemia.