incretins and Bone-Diseases--Metabolic

There are two kinds of incretin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) . GIP directly affects osteoblasts and osteoclasts, resulting in increasing bone mass by enhancing bone formation and suppressing bone resorption. On the other hand, GLP-1 does not affect bone directly. GLP-1 is reported to stimulate calcitonin secretion in thyroid gland and then indirectly increase bone mass. Dipeptidyl peptidase-4 inhibitors, which activate the function of incretin, may decrease the risk of osteoporotic fractures. In addition, it has been shown that osteoblast-derived osteocalcin stimulates GLP-1 secretion. Therefore, there may be an interaction between bone and digestive tract.

Topics: Animals; Bone and Bones; Bone Diseases, Metabolic; Glucagon-Like Peptide 1; Humans; Incretins; Life Style

Increased fat mass contributes to bone deterioration. Glucagon-like peptide 1 (GLP-1) and its related peptide exendin 1-39 amide (Ex-4), two lipid-lowering peptides, exert osteogenic effects in diabetic states. We examined the actions of 3-day administration of GLP-1 or Ex-4 on bone remodeling markers and on bone mass and structure in hyperlipidic (HL) and hypercaloric rats. Wistar rats on a hyperlipidemic diet for 35 days were subcutaneously administered GLP-1 (0.86  nmol/kg per h), Ex-4 (0.1  nmol/kg per h), or saline (control) by continuous infusion for 3 days. After killing, tibiae were removed for total RNA and protein isolation, as well as femurs and L1-L4 vertebrae for bone mass and quality assessment. Body weight and plasma insulin were unaltered in HL rats, which showed osteopenia (by dual-energy X-ray absorptiometry), associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. GLP-1 or Ex-4 administration decreased the levels of glucose, triglycerides, and total cholesterol in plasma but increased osteocalcin (OC) gene expression and the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio - at the expense of an augmented OPG - above corresponding control values in the tibia. Each tested peptide similarly reversed the decreased femoral and vertebral bone mass in these rats, whereas the deteriorated trabecular structure in the vertebrae improved associated with normalization of bone remodeling. These findings demonstrate that GLP-1 and Ex-4 are similarly efficient in reversing the bone alterations in this HL rat model, which has proven to be useful for studying the fat-bone relationships.

Topics: Animals; Biomarkers; Bone Density; Bone Diseases, Metabolic; Dietary Fats; Drug Evaluation, Preclinical; Exenatide; Glucagon-Like Peptide 1; Humans; Hyperlipidemias; Hypoglycemic Agents; Incretins; Lumbar Vertebrae; Osteogenesis; Peptides; Rats; Rats, Wistar; Venoms