Karsenty’s group has indicated that OCN-knockout mice display decreased β-cell proliferation, glucose intolerance, and insulin resistance. In ex vivo studies, when pancreatic β-cells isolated from wild-type mice were cocultured with wild-type osteoblasts or in the presence of supernatants from cultured osteoblasts, insulin secretion increased, suggesting the presence of an osteoblast-derived circulating factor that regulates β-cell function. Administration of OCN significantly decreased glycemia and increased insulin secretion. Furthermore, OCN function was exerted through adiponectin – coculture of wild-type osteoblasts with adipocytes increased adiponectin expression and action [100, 101]. A number of human studies have also explored the relationship between OCN and glucose homeostasis. OCN levels have been reported to be lower in T2D compared to healthy subjects [102], inversely related to body mass index, fat mass, and plasma glucose [103–106] but also to atherosclerosis and inflammatory parameters such as high sensitive C-reactive protein and IL-6 [107].
Ferron et al. have also shown that in mice fed with a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, with increased energy expenditure and improved insulin sensitivity.
Lifestyle Intervention
Lifestyle intervention is considered the golden standard for treating obesity and preventing cardiometabolic-related events. In a recent study, Villareal’s group has randomized 107 obese elderly subjects to control group, diet group, exercise group, and diet–exercise group for 1 year. At the end of the study, the diet–exercise and diet groups had similar improvements in insulin area under the curve (AUC), glucose AUC, visceral fat, tumor necrosis factor, and adiponectin while no changes in these parameters occurred in both exercise and control groups [108]. Importantly, the combination of these two interventions reduced insulin sensitivity and the cardiometabolic syndrome prevalence by 40 % [108]. These data confirmed previous findings showing that exercise training per se may have a neutral effect on insulin sensitivity while it becomes detrimental when associated to weight loss.
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