Long-term diabetes increases the chance of developing diabetic complications that is associated with significant morbidity and mortality. Even though all organ systems can be affected by diabetes, the four most common complications of diabetes are macrovascular disease, nephropathy, retinopathy, and neuropathy. At Creative Biolabs, our diabetic complication platform provides validated rodent models of diabetic complications for the research and development of potential therapeutics for the disease.
Diabetic Nephropathy
Diabetes mellitus is a complex metabolic disorder of the endocrine system resulting from a defect in insulin secretion, insulin action, or a mixture of both. Diabetic nephropathy (DN) is a long-term major microvascular complication of both type 1 and type 2 diabetes, affecting a large population worldwide. Although factors such as hyperglycemia, hyperlipidemia, hypertension and proteinuria have been discovered to contribute to the progression of renal damage in DN, the exact pathogenesis is still unknown. To better elucidate the pathogenesis as well as to develop new treatments for these complications, rodent models are frequently used.
Diabetic Retinopathy
Diabetic retinopathy (DR) is a one of the most common microvascular complications of diabetes. It has been reported that about one-third of the diabetic patients have manifested signs of DR and about-one tenth of them even have vision-threatening retinopathy. A variety of animal models have been developed for a better understanding of the development of DR at the molecular and cellular levels. Both mouse and rat models of DR are available at Creative Biolabs, including pharmacologically-induced DR models by injection of STZ or alloxan, models carrying endogenous mutation (e.g., NOD mouse, KKAy, ZDF rats, OLETF rats) and proliferative retinopathy models (e.g., oxygen-induced retinopathy mouse models).
Fig.1 Proposed model of the pathogenesis of diabetic complications. (Sada et al. 2016)
Diabetic Neuropathy
Diabetic neuropathy is a shattering complication of diabetes and leading cause of foot exclusion. Clinical indications of diabetic neuropathy mainly include increased vibration and thermal perception thresholds that progress to sensory loss, occurring in conjunction with degeneration of all fiber types in the peripheral nerve. Some also describe abnormal sensations such as paresthesia, allodynia, hyperalgesia, and spontaneous pain that sometimes coexist with loss of normal sensory function. A number of diabetic models have been found to be suitable models of human diabetic neuropathy, including the db/db mice, STZ-induced C57BL6/J and ddY mice, spontaneously diabetic WBN/Kob rats, NOD mice, spontaneously induced Ins2 Akita mice, and ob/ob mice.
The prevention and treatment of diabetic complications is of great importance for the large population of patients with diabetes. Rodent models are valuable tools for providing insights on its pathophysiology and can be used for testing the efficacy and safety of different pharmacological therapies for the management of these complications. Diabetic complication mouse and rat models available at Creative Biolabs include but are not limited to:
Our Capabilities
Application of suitable techniques to analyze animal models of human diabetic complications is critical to study the efficacy of potential therapeutics. For the study of diabetic retinopathy, the vascular alterations will be monitored in the process of treatment over time using fundus photography (FP), electrophysiological testing, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). Eyes are sampled and subjected to histological analysis at the end of the experiment to study the retinal vasculature. Various molecular and biochemical techniques (e.g., quantitative PCR, microarray, western blotting, as well as protein, enzyme and cytokine assays) can be carried out to study the expression of various genes and proteins in the eyes. In murine models of diabetic neuropathy, tactile allodynia and thermal hyperalgesia are evaluated using hind paw withdrawal, Von Frey filaments, and tail-flick tests. Dysfunction of myelinated nerve fiber is indicated in electrophysiological motor nerve conduction velocity assays. Briefly, Creative Biolabs offers an extensive range of assessments, including but not limited to:
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Creative Biolabs has developed strong knowledge and expertise in efficacy studies of gene therapies, biologics, and small molecules. Diet- and chemically-induced diabetic rodent models, surgically-induced models as well as genetically modified mouse model are available for the study and development of diabetic complication. Contact our scientists to discuss your detailed research plan today.
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