The Diabetogenic Effects of Streptozotocin in Mice are Prolonged and Inversely Related to Age

Abstract

Single "subdiabetogenic" doses of streptozotocin (SZ), when given to young male CD-1 mice, produced a delayed onset of hyperglycemia dependent on the dose of SZ and on the age of the mice. The effect was markedly reduced or absent in older mice given the same dose of SZ per kg of body weight. Histologic examination of the pancreas of these animals revealed that SZ induced greater damage to the islets of the young mice compared with older mice. In addition to the characteristic findings of a decrease in insulin-containing cells and an increase in glucagon- and pancreatic polypeptide-containing cells there was evidence of new islet formation. Delayed-onset hyperglycemia was also induced in young inbred DBA/2J, C57BL/KsJ, and SWR/J mice with single SZ doses as well as with alloxan in young CD-1 mice, indicating that the effect was not specific for CD-1 mice not for SZ as the agent inducing beta-cell injury. The induction of beta-cell autoimmunity did not appear to be important in the delayed diabetogenic effect of SZ, since insulitis was rare and followed the onset of hyperglycemia when seen, and islet cell autoantibodies were not found. Rather, SZ induced more beta-cell destruction in young animals than in older mice, and the continued somatic growth of the former suggests that the delayed hyperglycemia was due to an out-growing of a reduced insulin supply. That mild to severe diabetes could be induced by the same dose of SZ/kg, depending only on the age of the mice when SZ was given, may have implications for understanding the apparent heterogeneity of human diabetes mellitus.

Switching-On Survival and Repair Response Programs in Islet Transplants by Bone Marrow–Derived Vasculogenic Cells

“…The vascular contribution of bone marrow-derived vasculogenic cells varies greatly in tumors of different origin and grades and in transplanted versus spontaneous tumors (9,20,22,35). These observations predict that recruitment and development of these progenitors may also differ among quiescent tissues.…”

“…Islets were cultured overnight in RPMI-10% FCS, handpicked, and transplanted under the kidney capsule. Diabetic mice were generated by intraperitoneal injection of a single dose of 200 mg/kg streptozotocin (22) and transplanted with islets 1 week later. Upon ensuing of frank hyperglycemia (i.e., 200 mg/dl), mice were injected subcutaneously with insulin (Humulin L; Lilly) up to 3 days after transplant.…”

P21cip-Overexpression in the Mouse β Cells Leads to the Improved Recovery from Streptozotocin-Induced Diabetes

“…As a specific β-cell toxin, streptozotocin can induce β-cell necrosis and diabetes when given as a single dose, and limited β-cell regeneration after STZ treatment has been reported [17], [18]. Double transgenic mice and control mice (single transgenic littermate) were supplemented with dox for 8 days, 9 days, 10 days or 14 days respectively, during our experiments to initiate and maintain P21 expression.…”

Type 2 Diabetes and the Aging Pancreatic Beta Cell

“…Streptozotocin (STZ) causes beta cell necrosis and diabetes after a single, high dose injection in adult mice, and beta cell regeneration following destruction has been well-established [37]. p16 Ink4a +/+, +/−, and −/− mice were injected with STZ, resulting in beta cell necrosis and diabetes in all genotypes.…”