Etude de l’effet du jeûne intermittent sur des paramètres biochimiques et organiques liés au métabolisme glucidique et lipidique chez des rats atteints du diabète de type 1 (Albinos albinos) et de type 2 (Psammomys obesus)

Abstract

Calories intake excess induces metabolic disturbances leading to the outcome of chronic diseases. Caloric restriction (CR) and intermittent fasting (IF) are two diet manipulations used to reverse the negative effect of calories overabundance. Several studies have proven effectiveness of these two paradigms to prevent development of many diseases such as diabetes. The intermittent fasting paradigm known as alternate day fasting (ADF) consists in total food deprivation for a full day that alternates with a “feast day” on which food is consumed ad libitum. The fast and feast periods are typically 24 h each, but they may vary. Our aim is to assess the effect of intermittent fasting mimic Ramadan fasting upon biochemical and organic parameters related to carbohydrate and lipid metabolism and which could be altered by diabetes conditions. This fasting consists of a daily intermittent fasting for 15 hours followed by ad libitum period, over 30 days. To fulfill our aim, we use animal models representing each one diabetic syndrome. We study the effect of intermittent fasting in Psammomys obesus and Albinos albinos rat developing respectively diabetes type 2 and 1. We induced diabetes in Psammomys by switching them from vegetable diet to hypercaloric one. Diabetes type 1 was induced in wistar rats by intraperitoneal injection of 65 mg/Kg. Each group of rats was divided in control and diabetic rats. After what, they were either submitted to intermittent fasting or continue to have free access to food over the 30 last days of experiment. Those undergoing fasting were deprived from food during 15 hours over a period of 30 days. Third STZ sub group were exposed to a restricted food supply comparable to that ingested by the intermittently fasting animals. Such a caloric restriction represented a 20% decrease in food intake in the control animals and a 40% decrease of food intake in the STZ rats. In Psammomys obesus, the postprandial glycemia was comparable in control and non-diabetic sand rats, and little affected by intermittent fasting in these animals. In diabetic rats, however, the postprandial glycemica increased over the last 30-day period in non-fasting animals, whilst it decreased in the intermittently fasting animals. An essentially comparable situation was documented during the IPGTT performed in non-diabetic and diabetic rats before the switch in food intake and at days 10, 20 and 29 of the last 30-day period. In this case, intermittent fasting prevented in both non-diabetic and diabetic animals, the progressive deterioration of glucose tolerance otherwise recorded in non-fasting sand rats. Plasma insulin decrease under fasting, in another hand insulin stores are somewhat replenished in pancreatic islets from fasting diabetic rats. Insulin resistance is improved by intermittent fasting through de decrease of HOMA. This decrease contributes to improve plasma triglyceride concentration and liver triglyceride content which thereby alter steatosis in non-diabetic and diabetic rats. In diabetic wistar rats, hyperglycemia persists even after fasting and CR. However, it remains less increased compared to that recorded in non-fasting diabetic wistar rats. This relative improvement is accompanied by a weak architectural restoration of islets which are destroyed by streptozotocin. However, Insulin secretion was improved neither by intermittent fasting nor by calorie restriction. Apoptosis seems decreased in Islets from IF and CR diabetic rats. This decrease averaged 46.5% and 30% respectively in fasting and calorie restricted diabetic rats comparing with relative values of 100% in non-fasting diabetic rats. Proximal tubular epithelial cells showed obvious changes with PAS-positive grains at the periphery of cytoplasm (Armanni-Ebstein cells). This change was especially prominent in the straight portion of proximal tubules. These changes seem to be less accentuated in diabetic fasting and calorie restricted rats. Finally, the present study reveals that an intermittent daily fast has some beneficial effect upon biochemical and organic parameters which were altered by diabetes. Type 2 diabetic rats seems respond more to this fasting than the type 1 diabetic rats. This is probably due to the high degree of alteration in type 1 diabetes. It is important to have a residual beta cells mass which may respond positively to regimen like intermittent fasting. Even slight improvements of glucid and lipid profile contribute at least to delay complication related to diabetes conditions.