Genotype Gly/Gly of the Arg16Gly polymorphism of the beta2-adrenergic receptor is associated with elevated fasting serum insulin concentrations, but not with acute insulin response to glucose, in type 2 diabetic patients.
The beta(2)-adrenergic receptor (B2AR) is expressed in pancreatic beta-cells and modulates insulin secretion. The purpose of the present study was to evaluate the influence of the Arg16Gly variant allele of B2AR on insulin secretion in patients with type 2 diabetes. We used minimal model analysis of the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) and polymerase chain reaction (PCR)-restriction fragment length polymorphism to examine differences of insulin secretion and insulin resistance among three genotypes. There were no significant differences in baseline clinical characteristics, HbA1c, uric acid, CRP or lipid profiles among the three groups. The Gly/Gly group had significantly higher levels of fasting insulin (38.2+/-4.7 pmol/l versus 23.6+/-3.5 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (1.90+/-0.19 versus 1.32+/-0.24), compared with the Arg/Arg group, but there were no significant differences in acute insulin response to glucose (AIRg) bolus, insulin sensitivity (Si), or glucose effectiveness (Sg) among the three genotypes. Several reports have speculated that the Gly16 allele of B2AR exhibits agonist-promoted downregulation, but our findings, elevated fasting insulin concentrations, and previous clinical studies of blood pressure and lypolysis are controversial. The direct mechanism by which the Gly16 allele of B2AR may influence insulin secretion of pancreatic beta-cells is unknown. Further studies of the expression of the allelic receptor in islet cells may help to resolve the role of B2AR in insulin secretion. However, increased sensitivity to catecholamine-induced lipolysis of the Gly allele promotes higher free fatty acids concentrations in the portal system, which could enhance the higher levels of fasting insulin.
Ikarashi
Tomoo
T
Division of Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, 1-754 Asahimachi-dori, 951-8510, Niigata, Japan.
Hanyu
Osamu
O
Maruyama
Seitaro
S
Souda
Satoshi
S
Kobayashi
Chiaki
C
Abe
Eri
E
Ukisu
Jyunko
J
Naganuma
Keiko
K
Suzuki
Akiko
A
Toya
Maki
M
Kaneko
Susumu
S
Suzuki
Katsunori
K
Nakagawa
Osamu
O
Aizawa
Yoshifusa
Y
D000368:Aged; D001120:Arginine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D005215:Fasting / Q000097:blood*; D005260:Female; D005838:Genotype; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D005998:Glycine; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D007328:Insulin; D018343:Receptors, Adrenergic, beta-2; D001120:Arginine; D005947:Glucose; D005998:Glycine