Insulin binding to isolated fat cells from rats rendered hyperthyroid by daily injections of T4 (1 mg/kg) for 5 days was approximately doubled. The Scatchard curves reflected a large increase in receptor number, as well as an elevation in affinity of the high affinity binding sites. The response to insulin of the fat cells, however, was not increased accordingly: glucose incorporation into lipid in the presence of insulin did not differ significantly from that observed in the control group, whereas the effect of insulin on the lipolytic response to isoprenaline (isoproterenol) was even reduced in the T4-treated animals. T4 treatment had thus dissociated insulin binding from the metabolic effects of insulin, since the increase in membrane receptors was not paralleled by an enhanced effect of the hormone. Since levels of serum insulin were increased in the treated animals, the increase in number of insulin receptors was not mediated by reduced exposure to insulin. Propranolol failed to fully antagonize the effect of T4 on insulin binding, and reserpine treatment even enhanced it. It seems unlikely, therefore, that the increase in insulin receptors of adipocytes results from an augmented response to endogenous catecholamines in T4-treated rats.

Diabetic retinopathy is the leading cause of vision loss in working-age individuals in the United States and is expected to continue growing with the increased prevalence of diabetes. Streptozotocin-induced hyperglycemia in rats is the most commonly used model for diabetic retinopathy. Previous studies have shown that this model can lead to different inflammatory changes in the retina depending on the strain of rat. Our previous work has shown that crystallin proteins, including members of the alpha- and beta/gamma-crystallin subfamilies, are upregulated in the STZ rat retina. Crystallin proteins have been implicated in a number of cellular processes, such as neuroprotection, non-native protein folding and vascular remodeling. In this current study, we have demonstrated that unlike other strain-dependent changes, such as inflammatory cytokines and growth factor levels, in the STZ rat, the protein upregulation of crystallins is consistent across the Brown Norway, Long-Evans and Sprague-Dawley rat strains in the context of diabetes. Taken together, these data illustrate the potential critical role played by crystallins, and especially alpha-crystallins, in the retina in the context of diabetes.

Diabetes and its related complications represent a major growing health concern and economic burden worldwide. Ocular manifestations of diabetes include cataractogenesis and retinopathy, the latter being the leading cause of blindness in the working-age population. Despite numerous studies and recent progress, the exact pathophysiology of the disease remains to be fully elucidated and development of new and improved therapeutic strategies for this chronic condition are greatly needed. Heat shock proteins (Hsps) are highly conserved families of proteins, which are generally regarded as protective molecules that play a wide variety of roles and can be expressed in response to different types of cellular stresses. In recent years, numerous studies have reported their implication in various ocular diseases including diabetic retinopathy. The present review focuses on the potential implication of Hsps in ocular diabetic complications and discusses their specific mechanisms of regulation with respect to their expression, functions and alteration during diabetes. The review will conclude by examining the potential of Hsps as therapeutic agents or targets for the treatment of diabetic retinopathy.