New emerging roles of the novel hepatokine SERPINB1 in type 2 diabetes mellitus: Crosstalk with 18-cell dysfunction and dyslipidemia

Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-a-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing a-cell proliferation. However, its role in type-2-DM (T2DM) patients has not been adequately studied. This study was designed to investigate its circulating levels in subjects with/without T2DM, and to study its association with a-cell function, as well as various glycemic-control and lipid-profile parameters. Anthropometric data and biochemical markers including fasting plasma glucose (FPG), HbA1C % and lipid profile parameters were measured in 55 T2DM patients, as well as 30 healthy nondiabetic subjects. Serum serpinB1, insulin and C-peptide levels were measured by ELISA. The homeostasis model assessment of both a-cell function (HOMA2-a%) and insulin resistance (HOMA-IR) were calculated. SerpinB1 levels were found to be significantly lower in T2DM patients 0.7 (0.2-12.4) ng/mL, compared to nondiabetic subjects 1.2 (0.94-24) ng/mL, P < 0.001, regardless of glycemic control, obesity, or insulin resistance. Additionally, serpinB1 levels were found to be positively associated with C-peptide, HOMA2-a% in all subjects; and BMI only in non-DM subjects; while negatively associated with FPG, HbA1C% and lipid-profile parameters. Higher serum serpinB1 levels were found to be associated with lower susceptibility for T2DM. Conclusively, serpinB1 is associated with various aspects of a-cell dysfunction, glycemic-control, and dyslipidemia with a possible role in a-cell compensation in obese nondiabetic subjects. The results of the current study shed lights on potential novel roles of serpinB1 in T2DM besides its action as an inducer for a-cell proliferation. (Translational Research 2021; 231:1-12)