Genetic Permissiveness and Dietary Glycemic Load Interact to Predict Type-II Diabetes in the Nile rat (Arvicanthis niloticus)

Abstract

Objective: The Nile rat (Arvicanthis niloticus) is a superior model for Type-II Diabetes Mellitus (T2DM) induced by diets with a high glycemic index (GI) and glycemic load (GLoad). To better define the age and gender attributes of diabetes in early stages of progression, weanling rats were fed a high carbohydrate (hiCHO) diet for between 2 to 10 weeks. Methods. Data from four experiments compared two diabetogenic semipurified diets (Diet 133 (60:20:20, as % energy from CHO, fat, protein with a high glycemic load (GLoad) of 224 per 2000 kcal) versus Diets 73MBS or 73MB (70:10:20 with or without sucrose and higher GLoads of 259 or 295, respectively). An epidemiological technique was used to stratify the diabetes into quintiles of blood glucose (Q1 to Q5), after 2-10 weeks of dietary induction in 654 rats. The related metagenetic physiological growth and metabolic outcomes were related to the degree of diabetes based on fasting blood glucose (FBG), random blood glucose (RBG), and oral glucose tolerance test (OGTT) at 30 minutes and 60 minutes. Results. Experiment 1 (Diet 73MBS) demonstrated that the diabetes begins aggressively in weanlings during the first 2 weeks of a hiCHO challenge, linking genetic permissiveness to diabetes susceptibility or resistance from an early age. In Experiment 2, ninety male Nile rats fed Diet 133 (60:20:20) for 10 weeks identified two quintiles of resistant rats (Q1,Q2) that lowered their RBG between 6 weeks and 10 weeks on diet, whereas Q3-Q5 became progressively more diabetic, suggesting an ongoing struggle for control over glucose metabolism, which either stabilized or not, depending on genetic permissiveness. Experiment 3 (32 males fed 70:10:20) and Experiment 4 (30 females fed 60:20:20) lasted 8 weeks and 3 weeks respectively, for gender and time comparisons. The most telling link between a quintile rank and diabetes risk was telegraphed by energy intake (kcal/day) that established the cumulative GLoad per rat for the entire trial, which was apparent from the first week of feeding. This genetic permissiveness associated with hyperphagia across quintiles was maintained throughout the study and was mirrored in body weight gain without appreciable differences in feed efficiency. This suggests that appetite and greater growth rate linked to a fiber-free high GLoad diet were the dominant factors driving the diabetes. Male rats fed the highest GLoad diet (Diet 73MB 70:10:20, GLoad 295 per 2000 kcal for 8 weeks in Experiment 3], ate more calories and developed diabetes even more aggressively, again emphasizing the Cumulative GLoad as a primary stressor for expressing the genetic permissiveness underlying the diabetes. Conclusion: Thus, the Nile rat model, unlike other rodents but similar to humans, represents a superior model for high GLoad, low-fiber diets that induce diabetes from an early age in a manner similar to the dietary paradigm underlying T2DM in humans, most likely originating in childhood.

Dietary Carbohydrate as Glycemic Load, Not Fat, Coupled with Genetic Permissiveness Favoring Rapid Growth and Extra Calories, Dictate Metabolic Syndrome and Diabetes Induction in Nile Rats (Arvicanthis niloticus)

“…The Nile rat, a diurnal North African desert rodent, develops ‘spontaneous’ diabetes when housed in captivity and fed typical commercial mouse/rat chow low in fiber, i.e., Lab Diet 5008; 65:8:27 as CHO:fat:protein %energy with 3% fiber. Furthermore, semi-purified hiCHO-low fat diets devoid of fiber, for example, 70:10:20 CHO:fat:protein %energy, actually accelerate and amplify diabetes, while supplementation of certain fibers or polyphenols deters it [ 1 , 35 , 37 ]. In essence, the young Nile rat is exquisitely prone to T2DM during growth when fed a hiCHO diet in the absence of fiber.…”

“…Previous Nile rat data have detailed how rapidly growing pups that ate the most food (as kcal/day), including a high glycemic index (GI) and thus, a high cumulative GLoad (cumGLoad), developed the most diabetes. Additionally, their susceptibility to diabetes was strongly related to apparent genetic permissiveness , coupled with the cumGL consumed during the course of the experiment [ 35 ]. Furthermore, fat quality or fat calories did not appear to have much effect within the normal range of intake, in keeping with the human condition [ 12 , 36 ].…”

Age and sex as confounding factors in the relationship between cardiac mitochondrial function and type 2 diabetes in the Nile Grass rat

“…The Nile Grass rat (NR), Arvicanthis niloticus, mimics the slow progression of T2DM and related complications observed in human [29][30][31]. An asset of this animal model is that no pharmacological agent or genetic manipulation is needed to induce the disease.…”

Maternal High-Fiber Diet Protects Offspring against Type 2 Diabetes

“…Nile rats ( Arvicanthis niloticus ), native to tropical Africa, have a diet primarily of leaves and stems supplemented with insects, seeds, and fruits. The diabetic Nile rat model presents a similar nutritional etiology and disease progression to type 2 diabetes in humans [ 20 , 21 , 22 , 23 ], and thus it is an exemplary model to study how nutritional imbalances contribute to the development of type 2 diabetes. In a laboratory environment, Nile rats readily develop diabetes when fed a standard rodent chow [ 22 ], thereby referred to as a diabetogenic diet (specifically in the context of the Nile rat).…”