Furthermore, hepatocyte nuclear factor 1‑alpha (HNF1A), signal transducer and activator of transcription 3 (STAT3) and glucocorticoid receptor (GR) were key transcription factors in T2DM.
To evaluate the safety, pharmacokinetics and pharmacodynamics of SAR425899, a novel polypeptide, active as an agonist at both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCR), in healthy volunteers and in overweight/obese patients with type 2 diabetes (T2D).
In contrast, A3669GGR carriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%, P=0.001) despite the higher levels of both serum morning (21.7±6 vs 27.3±8.6 μg/dl, P=0.009) and midnight cortisol (18.8±5.8 vs 24.0±8.0 μg/dl, P=0.01).
The NR3C1N363S variant is associated with obesity and overweight in a range of patient settings but is not associated with hypertension or type 2 diabetes.
Although several other mutations in the GR gene have been postulated as being relevant to the progression to type 2 diabetes and cardiovascular diseases, conflicting results makes it difficult to determine exactly what effect these GR variations have on metabolic syndrome incidence and progression.
In conclusion, the abnormal regulation of GCR mRNA is likely to play a significant role in the insulin resistance observed in obese patients with Type II diabetes.