Prolactin protects against diabetes induced by multiple low doses of streptozotocin in mice

Abstract

In earlier studies it has been shown that prolactin (PRL) is a stimulating factor for the immune system, and it has been suggested that PRL might antagonize immunosuppressive effects of glucocorticoids. PRL has been reported to affect the cytokine secretion pattern, by elevating cytokine gene expression in macrophages, after the onset of sepsis. It also promotes the antibody response in mice where it increases the production of interferon-(IFN-) and inhibits interleukin-1 (IL-1) production. Due to these properties, PRL might influence the development of autoimmune type 1 diabetes. The aim of the present study was to examine the effects of two drugs; PRL and bromocriptine (BC) in vivo on the development of hyperglycemia and pancreatic insulitis in mice treated with multiple doses of streptozotocin (STZ) (40 mg/kg body weight, i.p.). The dopaminergic agonist BC is known to inhibit PRL secretion. In another set of experiments, the direct effects of PRL on the function of pancreatic islets exposed to STZ in vitro were studied. Mice treated with STZ became gradually hyperglycemic, and concomitant treatment with PRL (4 mg/kg body weight) for 21 days significantly reduced the elevation in blood glucose levels from day 10 onwards (P<0·05). Morphologic examinations of the pancreas on day 21 of mice receiving STZ injections revealed a marked insulitis, but only moderate insulitis in the STZ treated animals given PRL. BC administration (10 mg/kg body weight) in combination with STZ did not significantly affect the elevation in blood glucose levels or the insulitis. PRL or BC administration alone did not change the serum glucose concentration. This study indicates that PRL may affect hyperglycemia in the early phase of autoimmune diabetes. We suggest that it might be due to counteraction of autoimmune immunologic mechanisms and/or enhancement of -cell regeneration.

STAT5 Activity in Pancreatic β-Cells Influences the Severity of Diabetes in Animal Models of Type 1 and 2 Diabetes

“…This is in agreement with in vitro studies showing that growth hormone abrogates cytokine-induced apoptosis in INS-1 cells through activation of STAT5 (15). Moreover, protection against STZ-induced diabetes was also observed in mice with transgenic expression of placental lactogen in ␤-cells (5,6) or by injection of prolactin (46). The mechanism for the protective effect of STAT5 against ␤-cell destruction may involve members of the Bcl-2 family, as growth hormone stimulates the ␤-cell expression of Bcl-X L (15), which is a target gene of STAT5 involved in antiapoptosis (47).…”

The immunosuppressive and protective ability of glucose-regulated protein 78 for improvement of alloimmunity in β cell transplantation

“…Diabetes was induced in Balb/c mice by intraperitoneal (i.p.) injection of STZ (Sigma) at 40 mg/kg for 5 consecutive days, as reported previously [22]. Diabetes was monitored by measurement of blood glucose (BG) concentration from the tail vein using a blood glucose device (Roche Accu Check III, Roche, Basel, Switzerland).…”

Prolactin regulation of the expression of TNF-α, IFN-γ and IL-10 by splenocytes in murine multiple low dose streptozotocin diabetes

“…Studies indicate that PRL may influence the Th1/Th2 balance and this may influence the development of autoimmune diseases [11]. In line with this, it was shown that administration of PRL could counteract hyperglycemia in mice treated with multiple low doses of streptozotocin (STZ) [12], which is a well characterized model of type 1 diabetes [13]. This could suggest that the influence of PRL on the immune system may convey a protective action against type 1 diabetes.…”