Urszula Razny, Anna Polus, Joanna Goralska, Anna Zdzienicka, Anna Gruca, Maria Kapusta, Maria Biela, Aldona Dembinska-Kiec, Bogdan Solnica and Malgorzata Malczewska-Malec
To evaluate the effect of insulin resistance in obesity on the expression in whole blood of mRNA and miRNA affecting bone homeostasis as well as to estimate the influence of oral glucose load (OGTT) on serum osteocalcin concentration in obese individuals with and without insulin resistance.
Carboxylated (cOC), undercarboxylated (ucOC) and total osteocalcin were measured by ELISA in the serum of obese subjects with insulin resistance (n = 41) and obese subjects without insulin resistance (n = 41) (control group) during OGTT. Analysis of gene expression (microarray) and miRNAs (real-time PCR) was performed in venous blood (representating samples) collected before OGTT from obese with insulin resistance and controls.
Obese subjects with insulin resistance (higher HOMA-IR and lower oral glucose insulin sensitivity index) presented significantly increased expression of WNT signalling inhibitors (DKK1, DKK2, SOST, SFRP1) and downregulation of the key factor in WNT signalling – β catenin participating in osteoblasts differentiation. Expression of miRNA involved in osteoblastogenesis was also inhibited (miR-29b, miR-181a, miR-210, miR-324-3p). During OGTT, contrary to the control group, subjects with insulin resistance presented suppression of cOC and total OC decrease after 1 and 2 h of oral glucose load.
Obese subjects with insulin resistance may have defects in osteoblastogenesis that was demonstrated via key signalling molecules mRNA downregulation, and increased expression of WNT antagonists as well as inhibition of expression of miRNA participating in the regulation of osteoblast differentiation. Disturbed osteoblastogenesis in insulin-resistant subjects results in the suppression of blood carboxylated and total osteocalcin decrease during OGTT.
Hanne L Gulseth, Ingrid M F Gjelstad, Audrey C Tiereny, Danielle McCarthy, Julie A Lovegrove, Catherine Defoort, Ellen E Blaak, Jose Lopez-Miranda, Aldona Dembinska-Kiec, Ulf Risérus, Helen M Roche, Christian A Drevon and Kåre I Birkeland
Impaired insulin secretion and action contribute to the development of type 2 diabetes. Dietary fat modification may improve insulin sensitivity, whereas the effect on insulin secretion is unclear. We investigated the effect of dietary fat modification on insulin secretion in subjects with the metabolic syndrome.
In a 12-week pan-European parallel, randomized controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to four isoenergetic diets: high-fat diets rich in saturated fat (HSFA) or monounsaturated fat (HMUFA) or low-fat, high-complex carbohydrate diets with (LFHCC n-3) or without (LFHCC control) 1.2 g/day of n-3 PUFA supplementation. Insulin secretion was estimated as acute insulin response to glucose (AIRg) and disposition index (DI), modeled from an intravenous glucose tolerance test.
There were no overall effect of the dietary intervention on AIRg and DI in the total cohort, in neither the high-fat nor LFHCC groups. We observed significant diet*fasting glucose category interactions for AIRg (P = 0.021) and DI (P = 0.001) in the high-fat groups. In subjects with normal fasting glucose and preserved first phase insulin secretion, the HMUFA diet increased, whereas the HSFA diet reduced AIRg (P = 0.015) and DI (P = 0.010).
The effects of dietary fat modification on insulin secretion were minor, and only evident in normoglycemic subjects. In this case, the HMUFA diet improved AIRg and DI, as compared to the HSFA diet.