Effects of streptozotocin diabetes, glucose, and insulin on the metabolism of type IV collagen and proteoglycan in murine basement membrane-forming EHS tumor tissue.

The influence of streptozotocin diabetes, glucose, and insulin on the metabolism of basement membrane collagen and proteoglycan was studied in the murine EHS tumor. No differences were found in the amino acid composition of tumors grown in diabetic and control mice, suggesting that the relative amount of collagen was not increased. Similarly, no significant differences were observed in any of the intracellular enzyme activities of collagen biosynthesis in the tumor tissue, but in diabetic mice, a significant increase was found in all four enzyme activities studied in the kidneys. High glucose concentrations increased total protein synthesis of the tumor tissue in vitro whereas insulin had no effect. Basement membrane collagen synthesis was also increased but to the same extent as protein synthesis in general. No qualitative changes were found in the pro-alpha 1(IV) and pro-alpha 2(IV) chains synthesized in vitro with or without insulin at different glucose concentrations. Hyperglycemia secondary to insulin deficiency may thus be responsible for the basement membrane thickening in diabetes but this cannot explain the relative increase in collagen content of these matrices. The incorporation of 35SO4 into proteoglycan in vitro was likewise increased at high glucose concentrations, indicating that the synthesis of this component may also be altered in diabetes.