Effect of All‐Trans Retinoic Acid on the Pancreas of Streptozotocin‐Induced Diabetic Rat

Abstract

All-trans Retinoic acid (atRA) is instructive for the development of endocrine pancreas and is an integral component of b-cell induction protocols. We showed that atRA induces glucose-responsive endocrine transdifferentiation of pleomorphic pancreatic ductal adenocarcinoma cells in vitro. This study aimed to detect the role of atRA in improving the histological changes of the pancreas in diabetic rats. Forty young male Wistar rats were used and divided into three groups. Group I: normal vehicle control (N 5 5). Group II: streptozotocin-induced diabetic rats (N 5 20) were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocininduced diabetic rats (N 5 15) treated with atRA (2.5 mg/kg/day), were followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed for light, electron microscopy and pancreatic insulin mRNA expression. Blood samples were assayed for the levels of glucose, insulin, and total peroxides. In the atRA-treated group, the number of the islets and the islet area significantly increased. Strong insulin-immunoreactive endocrine-like cells were observed nearby the pancreatic acini and the interlobular ducts. Interestingly, insulin-positive cells seemed to arise from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. Pancreatic insulin mRNA and blood indices were almost normalized. AtRA improved the histological changes of the pancreas and the blood indices in diabetic rats. Anat Rec, 299:334-351, 2016. V C 2015 Wiley Periodicals, Inc.

All‐trans retinoic acid improves pancreatic cell proliferation on induced type 1 diabetic rats

“…The increase in body weight in animal models highlights regulation of metabolic glucose and energy expenditure within the body. These results are consistent with previously reported effects of ATRA . These results open a possibility of exploring ATRA as a treatment for individuals with diabetes, which has also been previously shown to reduce insulin sensitivity .…”

“…Thus, the features of pancreatic cells were carefully examined. The distribution of Langerhans islet in diabetes‐induced rats ( Figure b ) is similar to previously reported by Eltony et al . Appearance, number and size of Langerhans islets indicate function of the β‐cells as producers of hormones, such as insulin, glucagon, and pancreatic polypeptide.…”

Effects of ATRA on diabetic rats with renal ischemia-reperfusion injury

“…Pancreatic β-cells, acinar and ductal cells gradually restore their normal appearance under ATRA treatment. What's more, insulin messenger RNA and serum indices almost normalize, which improves the histological changes of the pancreas and the serum indices in diabetic rats 3,4 . In addition, ATRA can affect the progression of diabetic nephropathy without causing any significant side effects and has a therapeutic effect on diabetic nephropathy 5 .…”

Vav1 Sustains the In Vitro Differentiation of Normal and Tumor Precursors to Insulin Producing Cells Induced by all-Trans Retinoic Acid (ATRA)

“…The relationship between retinoids deficiency and the appearance of Type 1 diabetes mellitus, caused by reduction of the β-cell mass and function [54] as well as the evidence of ATRA-in duced restoration of Langerhans islet into diabetic rats [55] substantiate the crucial role of retinoids in β-cell formation in vivo. It is intriguing that in recent years the therapeutic approach to diabetes mellitus have explored new tools for the restoration of fully functional β-cells based on a set of strategies which include differentiation of multipotent stem cells [56][57][58], expansion of existing pools of cells, either from donors or by differentiating stem cells, and trans-differentiation of exocrine and endocrine pancreatic cells other than β-cells [59].…”