Prolactin Induced beta cell line, INS-1 Proliferation

Prolactin, a hormone secreted by the pituitary gland is a non-trophic hormone that stimulates lactation. Production and secretion of prolactin is elevated during pregnancy, and the hormone has been recognized as a potent growth factor for pancreatic beta cells.  It has been demonstrated that prolactin activates the JAK/STAT signaling pathway in pancreatic beta cells.  In 2007, a study conducted by Hugl and Merger in Germany, studied the role of prolactin in the proliferation of glucose-dependent beta cell line, INS-1. 

INS-1 cells secrete insulin in a glucose dependent manner.  Glucose induces the activation of insulin receptor substrate – 4 (IRS-4) and protein kinase and triggers the elevation of intracellular Ca²⁺ and cAMP concentrations.

[3H]thymidine incorporation was used to determine INS-1 cell proliferation after stimulation with different glucose concentrations (0-15 mM) with or without 0.5-2.0 nM prolactin.   The results indicated that Prolactin (0.5-2 nM) stimulated INS-1cell proliferation up to 2.4-fold even in the absence of glucose (Figure 1). In the presence of physiological glucose concentrations (6 mM), the same effect is seen (Figure 1). Glucose in concentrations from 3 to 15 mM stimulated INS-1 cell proliferation in a concentration-dependent manner up to 23- fold compared to unstimulated controls, with a maximum at 15 mM glucose. Co-stimulation with glucose and 0.5-2 nM prolactin further increased cell proliferation. Maximum stimulation (a 48.6-fold increase) was observed in the presence of 6 mM glucose and 0.5 nM prolactin, whereas no significant additional effect could be demonstrated upon higher doses of prolactin; instead, a trend towards reduced proliferation was observed.

            

Figure 1. Different prolactin concentrations   stimulate [3H]thymidine incorporation in INS-1 cells at different glucose concentrations. Approximately 105 quiescent INS-1 cells/well were incubated for 24 h in RPMI 1640 medium containing 0.1% BSA, 0 or 6 mM glucose plus/minus 0.5-2 nM prolactin, then assessed for proliferation rate by [3H]thymidine incorporation. All experiments were done in triplicate on at least eight independent occasions. The data are presented as x- fold standardized value above the control observation in the absence of prolactin and glucose (i.e. 3,000- 4,000 cpm/105 cells), and depicted as a mean±SE (n=8).

* Significant differences (P<0.05) vs. control observation in the absence of prolactin.

Reference:

Sigrun R Hügl and Michael Merger.  2007.  Prolactin Stimulates Proliferation of the Glucose-Dependent Beta-Cell Line INS-1 via Different IRS-Proteins.  J Pancreas (Online).  8(6):739-752.