Acrylamide and Potential Risk of Diabetes Mellitus: Effects on Human Population, Glucose Metabolism and Beta-Cell Toxicity

Abstract

Diabetes mellitus is a frequent endocrine disorder characterized by hyperglycemia. Acrylamide (AA) is food contaminant formed during the high-temperature processing of food rich in carbohydrates and low in proteins. Recent human epidemiological studies have shown a potential association between AA exposure and the prevalence of diabetes in the general population. In male rats, AA treatment promoted pancreatic islet remodeling, which was determined by alpha-cell expansion and beta-cell reduction, while in female rats AA caused hyperglycemia and histopathological changes in pancreatic islets. In vitro and in vivo rodent model systems have revealed that AA induces oxidative stress in beta cells and that AA impairs glucose metabolism and the insulin signaling pathway. Animal studies have shown that diabetic rodents are more sensitive to acrylamide and that AA aggravates the diabetic state. In this review, we provide an overview of human epidemiological studies that examined the relation between AA exposure and glucose disorders. In addition, the effects of AA treatment on pancreatic islet structure, beta-cell function and glucose metabolism in animal models are comprehensively analyzed with an emphasis on sex-related responses. Furthermore, oxidative stress as a putative mechanism of AA-induced toxicity in beta cells is explored. Finally, we discuss the effects of AA on diabetics in a rodent model system.

Keywords: acrylamide; beta-cell toxicity; diabetes mellitus; glucose metabolism; human epidemiological studies; in vitro; in vivo; oxidative stress.

Figure 1

The chemical structure of acrylamide.

Figure 2

Insulin and glucagon immunohistochemically stained pancreatic islets of control and AA-treated rats. Male Wistar rats were treated with AA in doses of 25 mg/kg b.w./d and 50 mg/kg b.w./d; 400× light microscope magnification [58].

Figure 3

Hematoxylin and eosin (HE)-stained pancreatic islets of control and AA-treated rats. Male Wistar rats were treated with AA in doses of 25 mg/kg b.w./d and 50 mg/kg b.w./d; 400× light microscope magnification [58].

Figure 4

iNOS, CAT, SOD1, SOD2 and CYP2E1 immunohistochemically stained pancreatic islets of control and AA-treated rats. Male Wistar rats were treated with AA in doses of 25 mg/kg b.w./d and 50 mg/kg b.w./d; iNOS, inducible nitric oxide synthase; CAT, catalase; SOD, superoxide dismutase; CYP2E1, cytochrome P450 2E1; 400× light microscope magnification [72].

Figure 5

Mallory-Azan-stained pancreatic islets of control and AA-treated rats. Male Wistar rats were treated with AA in doses of 25 mg/kg b.w./d and 50 mg/kg b.w./d. Black arrows show dilated blood vessels; 400× light microscope magnification [72].