Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Abstract

Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

Figure 1

Rats of the Normal Control and High Fat Diabetic control groups at 10th weeks.

Figure 2

Time course changes of blood glucose level of NC (n = 8), HF-DC group (n = 7). Values are expressed as mean ± SD. ^∗∗∗ p < 0.001, NC versus HF-DC.

Figure 3

Time course changes in total cholesterol among experimental groups of NC (n = 8), HF-DC group (n = 7). Values are expressed as mean ± SD. ^∗∗ p < 0.01, ^∗∗∗ p < 0.001, NC versus HF-DC.

Figure 4

Time course changes in triglyceride of NC (n = 8), HF-DC group (n = 7). Values are expressed as mean ± SD. ^∗∗∗ p < 0.001, NC versus HF-DC.

Figure 5

Time course changes in CPK-MB of NC (n = 8), HF-DC group (n = 7). Values are expressed as mean ± SD. ^∗∗∗ p < 0.001, NC versus HF-DC.

Figure 6

Histopathological changes of the myocardium and aorta. (a) The NC group rat heart revealed the noninfarcted architecture of the myocardium. (b) The HF-DC group rats showed myofibril damage and demonstrated marked edema, confluent areas of myonecrosis separation of myofibers, congested blood vessels, and mild inflammation. (c) NC group rat aorta showed the normal architecture. (d) Histopathology of HF-DC aorta showed fat cell deposition in vessel wall (atherosclerosis).

Figure 7

Histopathological changes of the Pancreas. (a) The NC group of rats pancreas were characterized by an organized pattern and showed normal architecture of beta cell mass. (b) The HF-DC group of rat pancreas damaged islets of Langerhans and the atrophy of beta cells showed reduced beta cell mass. The arrow showed beta cell mass.

Figure 8

Histopathology of the liver. (a) The liver of the NC group rats shows normal architecture of central vein, peripheral vein, and hepatocytes. (b) The HF-DC group showed degeneration of hepatocyte and congestion in liver.

Figure 9

Histopathology of the kidney. (a) Histopathology of NC group kidney showed normal structure of the kidney. (b) The HF-DC group showed congestion of glomerulus, damaged tubules, inflammation, and cloudy degeneration in tubules.

Figure 10

Immunohistochemical localization of insulin. (a) Immunohistochemistry of NC group pancreas showed increased localization of insulin. (b) The HF-DC group showed decreased insulin localization and hence loss of beta cell functions.