Adiponutrin gene is regulated by insulin and glucose in human adipose tissue.
OBJECTIVE
Adiponutrin is a new transmembrane protein specifically expressed in adipose tissue. In obese subjects, short- or long-term calorie restriction diets were associated with a reduction in adiponutrin gene expression. Adiponut.rin mRNA level was previously shown to be negatively correlated with fasting glucose plasma levels and associated with insulin sensitivity of non-diabetic obese and non-obese subjects. The purpose of the present work was to get more insight into the regulation of adiponutrin gene expression by insulin and/or glucose using clamp studies and to examine its potential dysregulation in subjects with a deterioration of glucose homeostasis.


METHODS
Adiponutrin gene expression was quantified by reverse transcriptase-quantitative PCR in s.c. adipose tissue of healthy lean subjects after an euglycemic hyperinsulinemic clamp (EGHI), a hyperglycemic euinsulinemic clamp, and a hyperglycemic hyperinsulinemic (HGHI) clamp. Adiponutrin gene expression was also analyzed in patients with different levels of insulin resistance.


RESULTS
During EGHI, insulin infusion induced adiponutrin gene expression 8.4-fold (P = 0.008). Its expression was also induced by glucose infusion, although to a lesser extend (2.2-fold, P = 0.03). Infusion of both insulin and glucose (HGHI) had an additive effect on the adiponutrin expression (tenfold, P = 0.008). In a pathological context, adiponutrin gene was highly expressed in the adipose tissue of type-1 diabetic patients with chronic hyperglycemia compared with healthy subjects. Conversely, adiponutrin gene expression was significantly reduced in type-2 diabetics (P = 0.01), but remained moderately regulated in these patients after the EGHI clamp (2.5-fold increased).


CONCLUSIONS
These results suggest a strong relationship between adiponutrin expression, insulin sensitivity, and glucose metabolism in human adipose tissue.
Moldes
Marthe
M
Department of Endocrinology, Cancer and Metabolism, Institut Cochin, Paris F-75014, France, Inserm, U567, Paris F-75014, France.
Beauregard
Geneviève
G
Faraj
May
M
Peretti
Noël
N
Ducluzeau
Pierre-Henri
PH
Laville
Martine
M
Rabasa-Lhoret
Rémi
R
Vidal
Hubert
H
Clément
Karine
K
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000502:physiology*; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009765:Obesity / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007328:Insulin; D008565:Membrane Proteins; D012333:RNA, Messenger; C436316:adiponutrin; D005947:Glucose