C-peptide corrects hepatocellular dysfunction in a rat model of type 1 diabetes

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ORIGINAL ARTICLE

C-peptide corrects hepatocellular dysfunction in a rat model of type 1 diabetes Heba A. Abdel-Hamid 1

&

Elshymaa A. Abdel-Hakeem 1 & Nagwa M. Zenhom 2 & Nisreen D. M. Toni 3

Received: 17 December 2019 / Accepted: 25 May 2020 # University of Navarra 2020

Abstract C-peptide is gaining much interest recently due to its well-documented beneficial effects on multiple organ dysfunction induced by diabetes. Our study was designed to investigate the effect of C-peptide on hepatocellular dysfunction in diabetic rats. Wistar male rats were separated into four groups: control, diabetic, diabetic + insulin, and diabetic + C-peptide. Serum levels of glucose, insulin, and liver biomarkers were assessed. Liver sections were collected for histopathological examination and immunohistochemical assessment of tumor necrosis factor alpha (TNF-α). Oxidative stress markers and gene expression of inducible nitric oxide synthase (iNOS), transforming growth factor beta 1 (TGF-β1), and glucose-6-phosphatase (G6Pase) were also measured in liver tissues. C-peptide administration prevented hepatic dysfunction induced by diabetes to a similar extent as that of insulin which was confirmed microscopically. We concluded that C-peptide could be used as an alternative therapy to insulin to correct hepatocellular dysfunction associated with type 1 diabetes mellitus (T1DM). Keywords C-peptide . Insulin . Diabetes . Liver . Rat

Introduction Diabetes mellitus (DM) is considered the most common metabolic disorder and one of the leading causes of death worldwide. It is characterized by persistent hyperglycemia associated with abnormal carbohydrate, protein, and lipid metabolism [36]. Much attention is given to this chronic disease because of the associated serious complications such as nephropathy, retinopathy, vasculopathy, neuropathy, and cardiovascular

diseases, along with hepatopathy. Currently accessible data have revealed that DM is connected to a number of liver abnormalities, such as abnormally elevated liver enzymes, abnormal glycogen deposition, non-alcoholic fatty liver disease, fibrosis then cirrhosis and hepatocellular carcinoma [23]. It has been reported that the mortality rate from end-stage liver disease in diabetic cases is greater than those with cardiovascular diseases [1]. In the population-based Verona diabetes study, cirrhosis accounted for 4.4% of diabetes-related deaths.

Key points • C-peptide corrected hepatocellular dysfunction in type 1 diabetes mellitus (T1DM). • C-peptide emerges as a promising agent for better control of diabetic liver. • C-peptide arises as a future alternative to insulin in management of diabetic liver. * Heba A. Abdel-Hamid [email protected]; [email protected] Elshymaa A. Abdel-Hakeem [email protected]; [email protected] Nagwa M. Zenhom [email protected] Nisreen D. M. Toni [email protected]

1

Medical Physiology Department, Faculty of Medicine, Minia University, Minia, Egypt

2

Biochemistry Department, Faculty of Medicine, Minia University, Minia