Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy.

Inês Preguiça,Pedro Gomes,Sara Nunes,Flávio Reis,Sofia D Viana,André Alves,Rosa Fernandes

doi:10.3390/nu12010250

Abstract

Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions.

Highlights

Diabetes mellitus is considered one of the primary contributors to non-communicable diseases.Estimates from the International Diabetes Federation (IDF) suggest that the number of persons afflicted by this disease will rise from 463 million in the year of 2019 to 700 million by 2045 [1]
Consortium (AMDCC), that proposed the following 3 criteria for a desirable murine model of DN [75]: (1) more than 50% decline in glomerular filtration rate (GFR) over the lifespan of the animal, (2) greater than 10-fold increase in albuminuria compared with controls for that strain at the same age and gender, and (3) histopathology findings which include mesangial sclerosis (a 50% increase in mesangial volume), any degree of arteriolar hyalinosis, glomerular basement membrane (GBM) thickening (a >25% increase compared with baseline by electron microscopy morphometry), and tubulointerstitial fibrosis (Figure 1)
The SDT rat is a non-obese Type 2 diabetes mellitus (T2DM) model that when aged about 24 weeks old, develops renal lesions accompanied by increases in urine volume and renal function parameters, which progresses with aging to severe tubular lesions, diffuse, and nodular glomerular lesions [90]

Summary

Introduction

Diabetes mellitus is considered one of the primary contributors to non-communicable diseases. To obviate the gap between preclinical and clinical research, experimental models aimed to replicate diabetic microvasculature dysfunction should ideally emulate T2DM main stressors and mimic the orchestrated mechanisms underlying human diabetes progression [8,9]. Diet-induced rodent models of T2DM, whether alone or combined with genetic/chemical stressors, are paramount to more closely replicate human microvascular complications [15,16]. Western diets have been a usual choice due to their ability to replicate human unhealthy dietary patterns along with a more robust and reproducible animal phenotype. We intended to revisit diet-induced rodent models, whether alone or combined with genetic or chemical tools, to successfully replicate the main clinical features underlying classical diabetic microvascular complications

Diet-Induced Models of Diabetic Peripheral Neuropathy

Diet-Induced Models of Diabetic Retinopathy

Diet-Induced Models of Diabetic Nephropathy

Findings

Concluding Remarks