Circulating glucagon is associated with inflammatory mediators in metabolically compromised subjects

Abstract

Background: Acute phase mediators promote metabolic changes by modifying circulating hormones. However, there is virtually no data about the link between glucagon and inflammatory parameters in obesity-related chronic low-grade inflammation. Study design: We performed both cross-sectional and longitudinal (diet-induced weight loss) studies. Methods: Circulating glucagon concentrations (ELISA), parameters of glucose and lipid metabolism, interleukin 6 (IL6), and complement factor B (CFB) were analyzed in 316 subjects (250 men and 66 women). The effects of weight loss were investigated in an independent cohort of 20 subjects. Results: Circulating glucagon significantly correlated with glucose (rZ0.407, P!0.0001), HbAlc (rZ0.426, P!0.0001), fasting triglycerides (rZ0.356, PZ0.001), and parameters of innate immune response system such as IL6 (rZ0.342, PZ0.050) and CFB (rZ0.404, PZ0.002) in obese subjects with altered glucose tolerance, but not in individuals with normal glucose tolerance (NGT). In obese and NGT subjects, glucagon was associated with fasting triglycerides (rZ0.475, PZ0.003) and CFB (rZ0.624, PZ0.001). In obese subjects, glucagon (PZ0.019) and CFB (PZ0.002) independently contributed to 26% of fasting triglyceride variance (P!0.0001) after controlling for the effects of age and fasting serum glucose concentration in multiple lineal regression models. Moreover, concomitant with fat mass, fasting triglycerides, and CFB, weight loss led to significantly decreased circulating glucagon (K23.1%, PZ0.004). Conclusions: According to the current results, acute phase reactants such as IL6 and CFB are associated with fasting glucagon in metabolically compromised subjects. This suggests that glucagon may be behind the association between inflammatory and metabolic parameters in obesity-associated chronic low-grade inflammation.

Glucagon Stimulates Ghrelin Secretion Through the Activation of MAPK and EPAC and Potentiates the Effect of Norepinephrine

“…Next we found that glucagon stimulated ghrelin secretion and proghrelin mRNA production. Our use of glucagon in the low nanomolar range is representative of the fasting levels of circulating glucagon in humans (20) and has been used by other groups to study the effects of glucagon in vitro (21). The stimulatory effect of glucagon on ghrelin secretion that we observed was also demonstrated in models in which glucagon was directly perfused through the femoral vein (15) or in isolated stomachs (16).…”

Dynamic monitoring of glucagon secretion from living cells on a microfluidic chip

“…Commercial ELISAs have LODs of 0.3 to 10 pM (e.g., assays from BioVendor or RayBiotech). This concentration LOD is far lower than the 1 nM achieved here, making them more suitable for serum measurements, where glucagon concentrations are ~50 pM (but highly variable) [31]. In principle it would be possible to incorporate a preconcentration step to improve the concentration LOD of the CEIA.…”

Metabolic surgery: Action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature

“…The studies that have been done show somewhat conflicting results; there may be a trend towards increased glucagon production after malabsorptive procedures. Patients undergoing medical weight loss show decreased glucagon production (109–111). After AGB there is no change in glucagon production (68, 91, 93), and after SG there is evidence of both early increase (42, 94) and late decrease (44, 112).…”