Alterations in wound healing associated with diabetes mellitus traditionally have been attributed to micro- nad macrovascular complications. We are hypothesizing that the insulin resistance associated with noninsulin dependent diabetes mellitus (NIDDM) affects the epidermal keratinocyte altering its response to insulin and other growth factors resulting in slow healing of wounds. Two different strains of mice C57BL/KsJ and NOD, have been identified as diabetic and expressing clinical symptoms similar to those found in humans with noninsulin dependent diabetes (C57Bl/KsJ) and insulin dependent diabetes (NOD). The long term objective of this study is to determine if insulin resistance associated with NIDDM influences the metabolic and mitogenic response of ketatinocytes to insulin and other growth factors. The specific aims for phase one of this study are (a) to further characterize the binding of insulin and epidermal growth factor (EGF) to epidermal keratinocytes from adult C57BL/KsJ mice from both the diabetic (db/db) and nondiabetic (db/m) littermates; (b) to characterize the metabolic and mitogenic responses of the db/db and db/m mice to insulin and EGF; and (c) modify and improve the methodology and technology for growing adult keratinocytes in culture. The second phase of the study has as its aim a comparison of the findings from the C57BL/KsJ diabetic and nondiabetic mouse with those from the NODS diabetic mouse. Keratinocyte binding of the growth factors will be characterized using 125I-insulin binding and 125I-EGF binding. The metabolic responses to insulin and EGF will be characterized by using 2- deoxyglucose transport and a-aminoisobutyrate uptake studies. The mitogenic response to insulin and EGF will be determined using 3H-thymidine incorporation studies. The findings from the study could provide a basis for therapy in diabetic wounds as well as providing a model system to use in the in vitro study of other skin disorders.