Abstract
Type 2 diabetes is characterized by increased insulin resistance and impaired insulin secretion. Type 2 diabetes is also associated with low-grade inflammation and increased levels of proinflammatory cytokines such as TNF-TNF-has been shown to impair peripheral insulin signaling in vitro and in vivo. However, it is unclear whether TNF-may also affect endogenous glucose production (EGP) during fasting and glucose-stimulated insulin secretion (GSIS) in vivo. We hypothesized that low-dose TNF-would increase EGP and attenuate GSIS. Recombinant human TNF-or placebo was infused in healthy, nondiabetic young men (n = 10) during a 4-hour basal period followed by an intravenous glucose tolerance test (IVGTT). TNF-lowered insulin levels by 12% during the basal period (P < 0.05). In response to the IVGTT, insulin levels increased markedly in both trials, but there was no difference between trials. Compared to placebo, TNF-did not affect EGP during the basal period. Our results indicate that TNF-acutely lowers basal plasma insulin levels but does not impair GSIS. The mechanisms behind this are unknown but we suggest that it may be due to TNF-increasing clearance of insulin from plasma without impairing beta-cell function or hepatic insulin sensitivity.
| Original language | English |
|---|---|
| Article number | 295478 |
| Journal | Mediators of Inflammation |
| Volume | 2014 |
| Pages (from-to) | 1-7 |
| Number of pages | 7 |
| ISSN | 0962-9351 |
| DOIs | |
| Publication status | Published - 2014 |
Keywords
- Adult
- Blood Glucose
- Diabetes Mellitus, Type 2
- Double-Blind Method
- Glucose
- Glucose Tolerance Test
- Humans
- Insulin
- Insulin-Secreting Cells
- Male
- Recombinant Proteins
- Signal Transduction
- Tumor Necrosis Factor-alpha
- Young Adult
