Diabetes is a rapidly growing epidemic affecting millions of Americans and has been implicated in a number of devastating secondary complications. We previously demonstrated that type 2 diabetic rats exhibit vitamin D deficiency due to aberrant megalin-mediated endocytosis and excessive urinary excretion of 25-hydroxycholecalciferol (25D3) and vitamin D-binding protein (DBP). Here, we examined whether a model of type 1 diabetes [T1D; streptozotocin (STZ)-treated Sprague-Dawley rats] would similarly excrete abnormally high concentrations of 25D3 and DBP due to renal damage and compromised expression of megalin and its endocytic partner, disabled-2 (Dab2). Moreover, we tested whether feeding diabetic rats starch that is resistant to digestion could alleviate these abnormalities. Control (n = 12) rats were fed a standard, semipurified diet (AIN-93G) containing 55% total dietary starch and STZ-treated rats were fed the AIN-93G diet (n = 12) or a diet containing 55% high-amylose maize that is partially resistant to digestion [20% total dietary resistant starch (RS); n = 12] for 2 and 5 wk. The RS diet attenuated weight loss and polyuria in STZ-treated rats. Histology and immunohistochemistry revealed that dietary RS also attenuated the loss of Dab2 expression in renal proximal tubules. Moreover, urinary concentrations of both 25D3 and DBP were elevated ∼10-fold in STZ-treated rats (5 wk post STZ injection), which was virtually prevented by the RS. We also observed a ∼1.5-fold increase in megalin mRNA expression in STZ-treated rats, which was attenuated by feeding rats the RS diet for 2 wk. Taken together, these studies indicate that consumption of low-glycemic carbohydrates can attenuate disruption of vitamin D homeostasis in T1D through the rescue of megalin-mediated endocytosis in the kidney.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by pancreatic beta cell dysfunction, insulin deficiency and abnormal carbohydrate metabolism. Chronic hyperglycemia causes structural damage to the kidneys, resulting in ultrafiltration and imbalance of nutrients such as vitamin D and disruption of various proteins associated with methyl group metabolism and homocysteine regulation. Using streptozotocin (STZ)‐treated rats as a model of T1DM, we have demonstrated that dietary resistant starch (RS) attenuates many complications associated with T1DM including increased urinary excretion of 25,OH vitamin D and vitamin D binding protein. The focus of this study was to further characterize the impact of RS on vitamin D balance and methyl group metabolism in diabetic rats. Female rats (n=36) were randomly assigned to 1 of 3 groups: control, T1DM and T1DM + dietary RS. Control and T1DM rats were fed a standard cornstarch diet during the 8‐wk treatment period, whereas T1DM + RS groups were fed a high amylose cornstarch diet (36% resistant to digestion). T1DM rats exhibited polyuria, hyperglycemia, decreased urinary creatinine excretion (2.3 fold) and increased hepatic (1.2 fold) and renal (~2 fold) GNMT activity. Dietary RS attenuated these complications. Future research will focus on understanding the mechanism by which dietary RS promotes regulation of vitamin d and methyl group metabolism. Body characters no spaces: 1217 / Body characters with spaces: 1428 Total characters no spaces: 1455 Grant Funding Source: Supported by Plant Sciences Institute, Iowa State University

Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by abnormal carbohydrate metabolism and hyperglycemia owing to beta cell dysfunction and insulin deficiency. A serious complication of T1DM is diabetic nephropathy, which can result in vitamin D imbalance, characterized by the loss of 25‐OH‐vitamin D in the urine. Using streptozotocin (STZ)‐treated rats as a model of T1DM, we have demonstrated that cooked dietary resistant starch (RS) attenuates the weight loss associated with T1DM and prevents the loss of vitamin D binding protein and 25‐OH‐vitamin D in the urine. The focus of this study was to determine if uncooked dietary RS would produce similar effects in a STZ‐induced mouse model of T1DM. In this study, 18 female mice were randomly assigned to one of 3 treatment groups: control, T1DM, and T1DM + uncooked dietary RS. Control and T1DM mice were fed a standard cornstarch diet during the 6‐wk treatment period, whereas T1DM + RS group were fed a diet containing high amylose cornstarch (36% resistant to digestion). To date, we have observed similar results in the mouse model, including diminished weight loss owing to the positive effect of dietary RS. Future research will be directed toward understanding the mechanism underlying the impact of RS on maintaining vitamin D balance, owing to the potential prevention of diabetic nephropathy in type 1 diabetic mice.Support: Plant Sciences Institute, ISU.Grant Funding Source: Plant Sciences Institute, ISU