Characterization of the Nile Grass Rat as a Unique Model for Type 2 Diabetic Polyneuropathy

Abstract

Type 2 diabetes (T2D) has reached pandemic proportions worldwide. Almost half of T2D patients suffer from polyneuropathy that can present as paresthesia, hyperalgesia, allodynia, or hypoesthesia. Therapeutic treatment options are largely incomplete, suggesting new avenues of research are needed. Herein, we introduce the African Nile Grass rat (NGR), which develops T2D solely by diet manipulation, as a novel T2D polyneuropathy model. The purpose of this study was to first characterize T2D-induced polyneuropathy in the NGRs before highlighting their strength as a potential prediabetic model of T2D. NGRs with long-term T2D exhibit hallmark features of polyneuropathy such as decreased motor nerve conduction velocity, intraepidermal denervation, and hyposensitivity to noxious mechanical and thermal stimulation. At the dorsal root ganglia, T2D neurons have altered sodium channel expression, specifically increased Nav1.7 and Nav1.9, and their surrounding satellite glial cells express glial fibrillary acidic protein. Now that these T2D NGRs have been characterized and shown to have a similar presentation to human and other animal models of T2D, the strength of this diet-induced model can be exploited. The prediabetic changes can be observed over their long progression to develop T2D which may allow for a therapeutic window to prevent T2D before permanent damage occurs.

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

“…However, in captivity with abundant food and no predators, even the Nile rat fed rat chow slowly develops MetS that eventually evolves into T2DM with all the pertinent features of the human condition: insulin resistance, hyperinsulinemia, hypertension linked ultimately to kidney failure, elevated TG with decreased HDL, and eventually hyperglycemia and beta cell failure resulting in depressed insulin and end-stage diabetes that includes severe ketosis [12,13,14,59,60], peripheral polyneuropathy [61], and cardiovascular disease [60,62]. They are also useful in studying diabetic lesions of the eye, including cataracts and retinopathy [63,64,65,66] and eventual renal failure as a consequence of advanced diabetes [13,67].…”

Endoplasmic reticulum–mitochondria interplay in chronic pain: The calcium connection

“…156 Initially, patients with DM and preclinical rodent models of DM typically present with mechanical and thermal hypersensitivity. 157 Later disease stages are associated with hyposensitivity as a result of sensory fiber retractions from the skin. 158 Pain in DM follows a “glove and stocking” pattern in which distal limbs are affected first, followed by more proximal areas of the body.…”

Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome

“…The Nile Grass rat (NGR), Arvicanthis niloticus , has demonstrated itself to be a unique animal model for diet-induced Type 2 Diabetes Mellitus (T2DM) because the NGR exhibits many of the pathologic features of T2DM 26–38 . When fed a fiber-free carbohydrate-rich diet, or even a standard commercial rodent chow, its carbohydrate and energy metabolism becomes deranged, in a manner similar to Metabolic Syndrome (MetS) and T2DM in humans.…”

“…The weanling NGR that develops MetS, experiences hyperphagia and accelerated weight gain which evolves into T2DM within 8–10 weeks while fed a high carbohydrate diet (as opposed to its natural high fiber diet in its native environment). The MetS-T2DM syndrome in the NGR is also characterized by hyperinsulinemia, hyperglycemia, insulin resistance, hyperlipidemia and hepatic pathology resembling non-alcoholic fatty liver disease (NAFLD) in humans as well as developing renal pathology culminating in renal failure 26–38 . Few other animal models mimic the T2DM observed in humans with such similar pathologic features of T2DM, making the NGR model of MetS/T2DM a unique animal model.…”