Afh Pfeiffer

In vivo activity of 11β-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance

Introduction  Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA‐induced hepatic insulin resistance is mediated by increased activity of hepatic 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), accompanied by elevated hepatic cortisol levels.

Polymorphism within connective tissue growth factor (CTGF) gene strongly predicts the marker of the ß-cell mass in non diabetic subjects

Aims: Connective tissue growth factor (CTGF) is a key determinant of progressive pancreas fibrosis and is up-regulated in Type 2 diabetes mellitus (T2DM). Recent studies indicate that CTGF promotes fibrogenesis both by enhancing pancreatic stellate cells proliferation and by releasing proinflammatory cytokines. CTGF inactivation in mice compromises islet cell proliferation during embryogenesis. Methods: We investigated the effect of a common polymorphism rs9493150 located in the CTGF locus on diabetes risk in two independent German cohorts from the same geographical region. The association between CTGF polymorphism and a non-invasive marker of beta-cell mass, C-peptide to glucose ratio, was additionally investigated. Results: Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) cohort (n=1026) (OR=0.637, CI 0.387–1.050, p=0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam) (n=3049) cohort (RR=0.77 CI 0.49–1.20, p=0.249 for general model) we found a significant association with increased diabetes risk. The C-allele of rs9493150 was strongly associated with decreased C-peptide to glucose ratio at 0 and 30 minutes of the oral glucose load in the general MESYBEPO cohort, both when investigating all participants (n=886; p=0.005 and p=0.004, respectively) and the subcohort of non-diabetic subjects (n=739; p=0.004 and p=0.024, respectively). Conclusions: These results indicate that the polymorphism in 3′-region of CTGF gene strongly predicts a surrogate marker of beta cell mass in non-diabetic subjects, although no association with T2DM risk was found in two independent cohorts.