Cadmium exposure decreases fasting blood glucose levels and exacerbates type-2 diabetes in a mouse model

Abstract

Although the effects of cadmium (Cd) on the development of diabetes have been extensively investigated, the relationship between Cd exposure and the severity of established diabetes is unclear.Herein, we investigate the effects of long-term exposure to Cd in a streptozotocin-induced mouse model of type 2 diabetes and the underlying mechanism. MethodsC57BL/6 Mice were divided into the following four groups: 1) control group; 2) Cd-exposed group; 3) diabetic group; 4) Cd-exposed diabetic group. Cd exposure was established by the administration of 155 ppm CdCl 2 in drinking water. After 25 weeks of treatment, serum fasting glucose and insulin were measured. Meanwhile, the liver and pancreas specimens were sectioned and stained with Hematoxylin and eosin. Gluconeogenesis, glycolysis, lactate concentration and brosis in liver were evaluated. ResultsClinical signs attributable to diabetes were more apparent in Cd-exposed diabetic mice. Interestingly, Cd exposure signi cantly decreased fasting blood glucose levels in diabetic group. We further demonstrated that the glycolysis related hepatic enzymes, pyruvate kinase M2 (PKM-2) and lactic dehydrogenase A (LDHA) were both increased, while the gluconeogenesis related hepatic enzymes, phosphoenolpyruvate-1 (PCK-1) and glucose-6-phosphatase (G6Pase) were both decreased in Cd exposed diabetic mice, indicating that Cd increased glycolysis and inhibited gluconeogenesis in diabetic model. Moreover, lactate accumulation was noted accompanied by the increased in ammation and brosis in the livers of diabetic mice following Cd exposure. ConclusionsCd exposure disturbed glucose metabolism and exacerbated diabetes, providing a biological relevance that DM patients are at greater risk when exposed to Cd. Materials And Methods Animal model and treatmentEight-week-old C57BL/6 male mice were purchased from the Experimental Animal Centre of Soochow University (Suzhou, China). All mice were housed ve per cage in poly-carbonate cages and maintained under a natural light/dark cycle at 18-28℃ and 40-60% humidity. After acclimatization to laboratory conditions for one week, the mice were fed by high fat diet (26.2% protein, 26.3% carbohydrate and 34.9% fat; Biopike company, D12492). Eight weeks later, mice were administered streptozotocin (STZ; 100mg/kg) once by intraperitoneal injection. One week later, mice with fasting blood glucose levels were measured by an automatic glucometer (Roche, Switzerland, ACCU-SHEK) and ≥16.7 mmol/L were de ned as T2DM mice. Mice were then subdivided into the following four groups: 1) non-diabetic mice (CON, n=10); 2) non-diabetic mice administered 155 ppm CdCl 2 in the drinking water (Cd, n=10); 3) diabetic mice (DM, n=15); 4) diabetic mice administered 155 ppm CdCl 2 in the drinking water (DM+Cd,

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“…Hyperglycemia and DM eventually occur in this vicious circle. 27 In this study, insulin increased GLUT-2 expressions, but when adding TNF-α with insulin, the levels of IR, GLUT-2, GCK, and PK were diminished, and the level of PEPCK was increased by TNF-α. It demonstrated that TNF-α deteriorated glucose uptake and glucose metabolism.…”

Integrating Transcriptomics and Proteomics to Characterize the Intestinal Responses to Cadmium Exposure Using a Piglet Model

“…For the carbohydrate metabolism, the CdCl 2 and Cdcr exhibited a differently enriched diabetes pathway. In vitro and in vivo studies have shown that Cd exposure interferes with the expression of metabolic pathways and related enzymes in glycolysis [ 72 , 73 ], glutamine [ 73 ], and the TCA cycle [ 74 ]. Meanwhile, a longitudinal prospective study also showed that Cd exposure significantly increased fasting glucose and T2DM prevalence [ 75 ].…”

SXRF for Studying the Distribution of Trace Metals in the Pancreas and Liver

“…The role of cadmium, iron and chromium in the regulation of insulin homeostasis is not that notable and/or still needs to be explored. Recent reports showed that cadmium exposure decreases fasting blood glucose levels and exacerbates type 2 diabetes in mice [ 51 ], while cadmium selectively accumulates in pancreatic islets, thus altering islet function, and, likely contributing to dysglycemia [ 52 ]. Iron overload is a risk factor for diabetes.…”