Glucagon in Women With Polycystic Ovary Syndrome (Pco): Relationship to Abnormalities of Insulin and Androgens

Abstract

SUMMARY To investigate the glucagon status of women with polycystic ovary syndrome (PCO) and to relate this to serum concentrations of insulin, androgens and SHBG, 44 women with PCO and 23 control subjects underwent a 75‐g oral glucose tolerance test. Although obese (body mass index > 30kg/m2) women with PCO had higher concentrations of glucose and insulin than overweight (BMI 25‐30kg/m2) and non‐obese (BMI <25kg/m2) women with PCO and control subjects, fasting and summed values of glucagon in response to oral glucose were similar in all groups. The fasting and summed concentrations of glucagon were inversely related to those of testosterone and androstenedione in obese women with PCO, but no other relationships were demonstrated between hormone values and those of glucagon in the other groups. We conclude that glucagon is not implicated in peripheral insulin resistance in women with PCO.

Abnormal CFTR Affects Glucagon Production by Islet α Cells in Cystic Fibrosis and Polycystic Ovarian Syndrome

“…This observation further supports a suppressive role of CFTR in glucagon production. More interestingly, the present finding provides an explanation to the clinically observed inverse relationship between androgens and glucagon levels (Golland et al, 1990 ). The upregulation of CFTR observed in PCOS model and induced by DHT in α cells, together with the suppressed blood glucagon/glucose levels in PCOS model and DHT-suppressed glucagon release by α cells, which can be reversed by CFTR inhibitors, suggest that the impaired glucagon levels observed in PCOS patients are likely to be due to the hyperandrogenism-induced upregulation of CFTR, since hyperandrogenism is a hallmark of PCOS (Gambineri et al, 2002 ; Azziz et al, 2006 ).…”

“…We further tested the role of CFTR in regulating glucagon levels in PCOS, a condition known to have defective glucose metabolism and exhibit reciprocal relationship between glucagon and androgen levels (Golland et al, 1990 ). We established a rat PCOS model by chronic DHT treatment according to previous reports (see section Materials and Methods).…”

“…Interestingly, CFTR expression can be upregulated by testosterone in prostate cancer (Xie et al, 2013 ). In PCOS, the fasting blood glucagon concentration is reported to be inversely related to androgen levels (Golland et al, 1990 ). Together with the findings that CFTR modulates p-CREB expression and downstream targets in ovarian granulosa cells in both CF and PCOS (Chen et al, 2012 ), we hypothesized that CFTR may be involved in the regulation of glucagon production by modulating p-CREB in α cells, and that defect or expression alteration of CFTR may dysregulate the glucagon levels, contributing to abnormal glucose levels as seen in CF and PCOS.…”