Receptors and effects of gut hormones in three osteoblastic cell lines

Pacheco‐Pantoja, Elda; Ranganath, L.; Gallagher, James A.; Wilson, Peter J.; Fraser, William D.

doi:10.1186/1472-6793-11-12

Cited by 139 publications

(113 citation statements)

References 50 publications

(82 reference statements)

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“…It has been reported that GLP-1 might directly stimulate in vitro osteoblastic cells via a specific GLP-1 receptor, different or similar to the one expressed in the pancreas. While murine MC3T3 osteoblastic cells were shown to express a GLP-1 receptor different from the cloned GLP-1 receptor in the pancreas (38), other human osteoblastic cell lines in contrast express the GLP-1R mRNA (40). This receptor is also expressed in the osteocytic cell line MLO-Y4 and in osteocytes in vitro and in situ (35) but was not detected in primary osteoblasts and osteoclasts cultured on plastic using qPCR (30).…”

Section: Discussionmentioning

confidence: 94%

“…While previous in vivo studies indicate indirect effects of GLP-1 on the skeleton via a calcitonin-dependent pathway (29), it has recently been shown that mouse osteoblast-like MC3T3-E1 cells express a functional receptor for GLP-1, different from the cAMP-linked GLP-1R expressed in the pancreas, suggesting a possible direct skeletal action of GLP-1 (38,39). In contrast, expression of the pancreatic-type GLP-1R mRNA was identified in human osteoblastic cell lines, although its expression varied between them (40). The presence of pancreatic GLP-1R has also been reported in osteocytic MLO-Y4 cells and osteocytes in rat femurs (35), as well as in mesenchymal stem cells (41).…”

Section: Introductionmentioning

confidence: 99%

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Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Pereira

Jeyabalan

Jorgensen

et al. 2015

Bone

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Pereira

Jeyabalan

Jorgensen

et al. 2015

Bone

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“…There are GIP-specific receptors located on osteoblasts (25) and osteoclasts (26). GIP operates as an anabolic hormone in the bone, where it stimulates incorporation of meal-derived Ca 2+ into bone and bone building (13), and reduces bone absorption by inhibiting osteoclastic activity.…”

Section: Discussionmentioning

confidence: 99%

Chronic Reduction of GIP Secretion Alleviates Obesity and Insulin Resistance Under High-Fat Diet Conditions

et al. 2014

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Gastric inhibitory polypeptide (GIP) exhibits potent insulinotropic effects on b-cells and anabolic effects on bone formation and fat accumulation. We explored the impact of reduced GIP levels in vivo on glucose homeostasis, bone formation, and fat accumulation in a novel GIP-GFP knock-in (KI) mouse. We generated GIP-GFP KI mice with a truncated prepro-GIP gene. The phenotype was assessed in heterozygous and homozygous states in mice on a control fat diet and a high-fat diet (HFD) , and GIP gfp/gfp mice, while insulin secretion remained lower. GIP gfp/+ and GIP gfp/gfp mice showed reduced obesity and reduced insulin resistance, accompanied by higher fat oxidation and energy expenditure. GIP-reduced mice demonstrate that partial reduction of GIP does not extensively alter glucose tolerance, but it alleviates obesity and lessens the degree of insulin resistance under HFD conditions, suggesting a potential therapeutic value.Gastric inhibitory polypeptide (GIP) is a 42-amino acid polypeptide produced by enteroendocrine K cells, which are located mainly in the upper parts of the small intestine. Its main secretagogues are glucose and, even more intensely, fats that reach the intestinal lumen soon after food intake (1). Following secretion, the hormone exerts its effects through specific, G-protein-coupled receptors located mainly in the stomach, pancreas, central nervous system, bone, and adipose tissue (2,3). Apart from its role in the inhibition of gastric acid secretion (4), GIP exhibits potent glucose-dependent insulinotropic action (5,6), and, therefore, it is classified as an incretin (3). In addition to its insulinotropic effect, in the absence of which glucose intolerance develops (7), GIP stimulates islet growth (8) and proliferation of b-cells (9), and reduces b-cell apoptosis (10,11). Studies of GIP receptor (GIPR) knock-out (GIPRKO) mice (7) describe GIP as an obesitypromoting factor in high-fat diet (HFD) conditions, and show that deletion of GIPR signaling causes resistance to obesity (12) but leads to osteoporosis (13), revealing an important role of GIP in bone metabolism. However, in these studies, as well as in a model of GIPR antagonism (14), the reported changes were focused on disrupted or blocked GIPR signaling. The condition of reduced GIP secretion and how it affects the pancreatic and extrapancreatic effects of GIP remain unclear.The aim of the current study is to explore the potential of reduced GIP levels in vivo, and to define the impact on glucose homeostasis, bone formation, and fat accumulation in a novel GIP-green fluorescent protein (GFP) knock-in (KI) mouse model characterized by truncation of the prepro-GIP gene and insertion of a GFP sequence (15). The model was developed for the purpose of visualization and identification of K cells and exhibits reduced

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“…Despite a wide distribution of its receptor in the body, the most remarkable action of GIP is to potentiate glucose-stimulated insulin secretion from pancreatic β-cells [7]. Recently, the presence of a functional GIPR has been evidenced at the surface of osteoblasts and osteoclasts [8,9]. However, the role of GIP in bone physiology remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice

Gaudin-Audrain¹,

Irwin²,

Mansur³

et al. 2013

Bone

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A role for the gastro-intestinal tract in controlling bone remodeling is suspected since serum levels of bone remodeling markers are affected rapidly after a meal. Glucose-dependent insulinotropic polypeptide (GIP) represents a suitable candidate in mediating this effect. The aim of the present study was to investigate the effect of total inhibition of GIP signaling on trabecular bone volume, microarchitecture and quality. We used GIP receptor (GIPR) knockout mice and investigated trabecular bone volume and microarchitecture by microCT and histomorphometry. GIPR-deficient animals at 16 weeks of age presented with a significant (20%) increase in trabecular bone mass accompanied by an increase (17%) in trabecular number. In addition, the number of osteoclasts and bone formation rate was significantly reduced and augmented, respectively in these animals when compared with wild-type littermates. These modifications of trabecular bone microarchitecture are linked to a remodeling in the expression pattern of adipokines in the GIPR-deficient mice. On the other hand, despite significant enhancement in bone volume, intrinsic mechanical properties of the bone matrix was reduced as well as the distribution of bone mineral density and the ratio of mature/immature collagen cross-links. Taken together, these results indicate an increase in trabecular bone volume in GIPR KO animals associated with a reduction in bone quality.

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Receptors and effects of gut hormones in three osteoblastic cell lines

Cited by 139 publications

References 50 publications

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Chronic Reduction of GIP Secretion Alleviates Obesity and Insulin Resistance Under High-Fat Diet Conditions

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice

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