Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states.
It has been suggested that hormones released after nutrient absorption, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2), could be responsible for changes in bone resorption. However, information about the role of GLP-1 in this regard is scanty. Diabetes-related bone loss occurs as a consequence of poor control of glucose homeostasis, but the relationship between osteoporosis and type 2 diabetes remains unclear. Since GLP-1 is decreased in the latter condition, we evaluated some bone characteristics in streptozotocin-induced type 2 diabetic (T2D) and fructose-induced insulin-resistant (IR) rat models compared to normal (N) and the effect of GLP-1 or saline (control) treatment (3 days by osmotic pump). Blood was taken before and after treatment for plasma measurements; tibiae and femora were collected for gene expression of bone markers (RT-PCR) and structure (microCT) analysis. Compared to N, plasma glucose and insulin were, respectively, higher and lower in T2D; osteocalcin (OC) and tartrate-resistant alkaline phosphatase 5b were lower; phosphate in IR showed a tendency to be higher; PTH was not different in T2D and IR; all parameters were unchanged after GLP-1 infusion. Bone OC, osteoprotegerin (OPG) and RANKL mRNA were lower in T2D and IR; GLP-1 increased OC and OPG in all groups and RANKL in T2D. Compared to N, trabecular bone parameters showed an increased degree of anisotropy in T2D and IR, which was reduced after GLP-1. These findings show an insulin-independent anabolic effect of GLP-1 and suggest that GLP-1 could be a useful therapeutic agent for improving the deficient bone formation and bone structure associated with glucose intolerance.
Nuche-Berenguer
Bernardo
B
Department of Metabolism, Nutrition, and Hormones, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, Madrid, Spain.
Moreno
Paola
P
Esbrit
Pedro
P
Dapía
Sonia
S
Caeiro
José R
JR
Cancelas
Jesús
J
Haro-Mora
Juan J
JJ
Villanueva-Peñacarrillo
María L
ML
D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007527:Isoenzymes / Q000097:blood; D008297:Male; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism / Q000627:therapeutic use*; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000071681:Tartrate-Resistant Acid Phosphatase
D007328:Insulin; D007527:Isoenzymes; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D053245:RANK Ligand; D015675:Osteocalcin; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D005947:Glucose