Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus): a novel model for diet-induced type 2 diabetes and the metabolic syndrome

Abstract

BackgroundThe prevalence of Metabolic Syndrome and related chronic diseases, among them non-insulin-dependent (type 2) diabetes mellitus, are on the rise in the United States and throughout the world. Animal models that respond to environmental stressors, such as diet, are useful for investigating the outcome and development of these related diseases.ObjectiveWithin this context, growth and energy relationships were characterized in the Nile rat, an exotic African rodent, as a potential animal model for diet-induced type 2 diabetes mellitus and Metabolic Syndrome.MethodsCompiled data from several studies established the relationship between age, body weight gain (including abdominal adiposity), food and water consumption, and blood glucose levels as determinants of diabetes in male and female Nile rats. Glucose Tolerance Testing, insulin, HbA1c, blood pressure measurements and plasma lipids further characterized the diabetes in relation to criteria of the Metabolic Syndrome, while diet modification with high-fat, low-fiber or food restriction attempted to modulate the disease.ResultsThe Nile rat fed lab chow demonstrates signs of the Metabolic Syndrome that evolve into diet-induced non-insulin-dependent (type 2) diabetes mellitus characterized by hyperinsulinemia with rising blood glucose (insulin resistance), abdominal adiposity, and impaired glucose clearance that precedes increased food and water intake, as well as elevated HbA1c, marked elevation in plasma triglycerides and cholesterol, microalbuminuria, and hypertension. Males are more prone than females with rapid progression to diabetes depending on the challenge diet. In males diabetes segregated into early-onset and late-onset groups, the former related to more rapid growth and greater growth efficiency for the calories consumed. Interestingly, no correlation was found between blood glucose and body mass index (overall adiposity) in older male Nile rats in long term studies, whereas blood glucose and the perirenal fat pad, as well as liver and kidney weight, were positively related to early-onset diabetes. Rats weaned early (4-5 wks) and challenged with a high-fat Western-type diet developed diabetes faster, and body fat accumulation was more apparent, whereas food restriction curtailed it.ConclusionThe Nile rat fed typical rodent diets develops hyperinsulinemia that precedes hyperglycemia (insulin resistance) leading to diet-induced type 2 diabetes associated with hypertriglyceridemia, hypercholesterolemia, and hypertension. Dietary modulation affected growth rate (weight gain and central adiposity) to impact disease progression. This rodent model represents a novel system of gene-diet interactions affecting energy utilization that can provide insight into the prevention and treatment of the type 2 diabetes and Metabolic Syndrome.

Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes

“…We investigated the effects of feeding highfiber (Hfib) versus lowfiber (chow) commercial rodent diets on the body composition of a recently described model of spontaneous T2D (Chaabo et al 2010); data given in Table 2. Chowfed Nile rats exhibited higher body weight at all ages (2, 6, and 12 months).…”

“…(i) Diabetes develops spontaneously on chow diet; native diet consists of predominantly flowering plants and seeds (Rabiu & Rose 1997). In captivity and fed standard rodent diets (higher in calories and lower in fiber compared with their native diet), they develop a metabolic syndromelike phenotype characterized by hyperinsulinemia preceding hyperglycemia (insulin resistance), as well as other landmark features of metabolic syndrome, including abdominal adiposity and weight gain, increased plasma triglycerides, and elevated cholesterol and hypertension (Chaabo et al 2010). Within 1 year, hyperglycemia worsens and is associated with glucosuria and eventually ketonuria.…”

“…Islets of Nile rats are described as degenerated (Noda et al 2010), and the concentrations of fed plasma insulin are reported to first compensate for, and then fail to respond to glucose (Chaabo et al 2010). Dietary manipulation such as caloric restriction or reduction of the energy density of food reduces diabetes incidence (Chaabo et al 2010).…”

Maternal Caloric Restriction prior to Pregnancy Increases the Body Weight of the Second-Generation Male Offspring and Shortens Their Longevity in Rats

“…Animal research shows that a spare diet from a young age might be helpful in preventing age induced damage on pancreatic β cells (He et al 2012). Unfortunately, there is still little knowledge on the ideal nutritional conditions following prenatal undernutrition, but it seems that high-energy postnatal diets are not among the best choices (Ozanne and Hales 2004;Benyshek et al 2004;Chaabo et al 2010). Others argue that maternal nutrition before pregnancy should be a key period for interventions (Wells 2003) since an inadequate maternal capital might still induce an energy saving mechanism responsible for future obesity and risk of premature death, as the present study showed.…”

Development of Improved Animal Models for the Study of Diabetes

“…Sex predilection was observed in males, which present segregation in two groups: early-onset diabetes and lateonset diabetes. Dietary modulation (high-fat diet) induce the early onset, as well as more accumulation of body fat [159].…”