Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia

Fitzgerald, Ryan T.; Olsen, Andrew; Nguyen, Jessica; Wong, Way W.; Muayed, Malek El; Edwards, Joshua R.

doi:10.3390/ijms22010360

Cited by 29 publications

(21 citation statements)

References 45 publications

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“…Thus, Cd-induced nephropathy may contribute, in part, to an elevation of plasma glucose levels among the subjects in the present study, which accentuates the central role of kidneys in the maintenance of plasma glucose levels [ 52 , 53 ]. These notions are in line with experimental studies in rats, where daily subcutaneous doses of Cd at 0.6 mg/kg for 12 weeks caused proteinuria [ 54 ], and hyperglycemia [ 55 ]. Half of the subjects in the present study were diagnosed with type 2 diabetes ( Table 2 ), and those with Cd and Pb exposure profiles 2 and 3 faced a 3–4.2-fold increment in the likelihood of having a diabetes diagnosis ( p = 0.002−0.009), while subjects with low eGFR were 2.9-times more likely to be diagnosed with diabetes.…”

Section: Discussionsupporting

confidence: 80%

Effects of Environmental Exposure to Cadmium and Lead on the Risks of Diabetes and Kidney Dysfunction

Yimthiang

Pouyfung

Khamphaya

et al. 2022

IJERPH

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Environmental exposure to cadmium (Cd) or lead (Pb) is independently associated with increased risks of type 2 diabetes, and chronic kidney disease. The aim of this study was to examine the effects of concurrent exposure to these toxic metals on the risks of diabetes and kidney functional impairment. The Cd and Pb exposure levels among study subjects were low to moderate, evident from the means for blood concentrations of Cd and Pb ([Cd]b and [Pb]b) of 0.59 µg/L and 4.67 µg/dL, respectively. Of 176 study subjects (mean age 60), 71 (40.3%) had abnormally high fasting plasma glucose levels. Based on their [Cd]b and [Pb]b, 53, 71, and 52 subjects were assigned to Cd and Pb exposure profiles 1, 2, and 3, respectively. The diagnosis of diabetes was increased by 4.2-fold in those with an exposure profile 3 (p = 0.002), and by 2.9-fold in those with the estimated glomerular filtration (eGFR) ≤ 60 mL/min/1.73 m2 (p = 0.029). The prevalence odds ratio (POR) for albuminuria was increased by 5-fold in those with plasma glucose levels above kidney threshold of 180 mg/dL (p = 0.014), and by 3.1-fold in those with low eGFR) (p = 0.050). Collectively, these findings suggest that the Cd and Pb exposure profiles equally impact kidney function and diabetes risk.

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Section: Discussionsupporting

confidence: 80%

Effects of Environmental Exposure to Cadmium and Lead on the Risks of Diabetes and Kidney Dysfunction

Yimthiang

Pouyfung

Khamphaya

et al. 2022

IJERPH

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“…Prior research in animal models identi ed a dysregulation of glucose metabolism, speci cally, a relationship between Cd exposure and increased blood glucose levels [5,6]. As reported, Cd exposure induced hyperglycemia, altered oxidative status and led to pancreatic β-cell dysfunction [7][8][9][10]. Our research group also found that Cd decreased serum insulin concentrations and induced insulin resistance [11].…”

Section: Introductionsupporting

confidence: 61%

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

Wang²,

Liu

et al. 2022

Endocrine

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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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“…However, it should be noted that not all studies have found significant associations between markers of Cd exposure and diabetes mellitus [ 8 ]. Numerous short-term and long-term in vivo Cd exposure models have shown Cd to cause hyperglycemia and disrupt glucose homeostasis in experimental animals [ 9 , 10 , 11 ]. The exact mechanism of action of the Cd-induced disruption of glucose homeostasis is unknown.…”

Section: Introductionmentioning

confidence: 99%

Diabetogenic and Obesogenic Effects of Cadmium in Db/Db Mice and Rats at a Clinically Relevant Level of Exposure

Nguyen

Patel

Gensburg

et al. 2022

Toxics

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Studies show an association between cadmium (Cd) exposure and prediabetes or type II diabetes mellitus. We have previously reported that Cd causes decreased levels of serum leptin in rats following 12 weeks of daily Cd dosing (0.6 mg/kg/b.w./day). Since leptin plays an important role in metabolism, we examined the effects of Cd on rats and db/db mice, which are deficient in leptin receptor activity. We gave rats and mice daily subcutaneous injections of saline (control) or CdCl2 at a dose of 0.6 mg/kg of Cd for 2 weeks, followed by 2 weeks of no dosing. At the end of the 4-week study, exposure to Cd resulted in a more rapid increase in blood glucose levels following an oral glucose tolerance test in db/db vs. lean mice. During the two weeks of no Cd dosing, individual rat bodyweight gain was greater (p ≤ 0.05) in Cd-treated animals. At this time point, the combined epididymal and retroperitoneal fat pad weight was significantly greater (p ≤ 0.05) in the Cd-treated lean mice compared to saline-treated controls. Although this pilot study had relatively low N values (4 per treatment group for mice and 6 for rats) the results show that clinically relevant levels of Cd exposure resulted in diabetogenic as well as obesogenic effects.

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Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia

Cited by 29 publications

References 45 publications

Effects of Environmental Exposure to Cadmium and Lead on the Risks of Diabetes and Kidney Dysfunction

Effects of Environmental Exposure to Cadmium and Lead on the Risks of Diabetes and Kidney Dysfunction

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

Diabetogenic and Obesogenic Effects of Cadmium in Db/Db Mice and Rats at a Clinically Relevant Level of Exposure

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