Vijay Yadav - Academia.edu (original) (raw)

Papers by Vijay Yadav

Research paper thumbnail of The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity

Journal of Cell Biology, 2008

Research paper thumbnail of An Osteoblast-dependent Mechanism Contributes to the Leptin Regulation of Insulin Secretion

Annals of The New York Academy of Sciences, 2009

Our work focuses on genetic and molecular mechanisms for the reciprocal regulation of bone and en... more Our work focuses on genetic and molecular mechanisms for the reciprocal regulation of bone and energy metabolism orchestrated by leptin and osteocalcin. In the context of this reciprocal regulation, the finding that leptin inhibits insulin secretion by β cells while osteocalcin favors it is surprising. In exploring the molecular bases of this paradox we found that leptin, as is the case for most of its functions, uses a neuronal relay to inhibit insulin secretion. Cell-specific gene-deletion experiments revealed that a component of this neuronal regulation is the sympathetic innervation to osteoblasts. Under the control of leptin the sympathetic tone favors expression in osteoblasts of Esp, which inhibits the metabolic activity of osteocalcin. We further identify ATF4 as a transcription factor that regulates Esp expression and thereby insulin secretion and sensitivity. Taken together these data illustrate the tight connections between bone remodeling and energy metabolism and add further credence to the notion that the osteoblast is a bona fide endocrine cell type.

Research paper thumbnail of Patients with high bone mass phenotype due to Lrp5-T253i mutation have low plasma levels of serotonin

Bone, 2010

The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to a... more The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex-and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean AE SEM: 2.16 AE 0.28 ng/mL versus 3.51 AE 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. ß

Research paper thumbnail of Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

Journal of Bone and Mineral Research, 2010

The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to a... more The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex-and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean AE SEM: 2.16 AE 0.28 ng/mL versus 3.51 AE 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. ß

Research paper thumbnail of Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

Journal of Bone and Mineral Research, 2010

The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to a... more The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex- and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean ± SEM: 2.16 ± 0.28 ng/mL versus 3.51 ± 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. © 2010 American Society for Bone and Mineral Research.

Research paper thumbnail of Divergent multiple carpometacarpal fracture dislocation

Journal of Orthopaedics and Traumatology, 2002

Multiple divergent dislocations of carpometacarpal joints are uncommon injuries. The Authors desc... more Multiple divergent dislocations of carpometacarpal joints are uncommon injuries. The Authors describe a heretofore unreported mediolateral divergence between the fourth and fifth rays coexisting with carpometacarpal dislocation that was reduced and retained by closed technique.

Research paper thumbnail of Unusual K-wire migration

Indian Journal of Pediatrics, 2006

The authors report a case of intra-abdominal migration of a Kirschner wire from the left hip to t... more The authors report a case of intra-abdominal migration of a Kirschner wire from the left hip to the right lobe of the liver in a 5-year-old child. The wire was used for stabilization of the left hip after open reduction for neglected unreduced congenital dislocation of the left hip. The migrated wire was removed by laparotomy. Surprisingly, no injury was noted to any intervening abdominal structure intra-operatively. This unusual migration of a Kirschner wire into a child’s liver has not been reported previously.

Research paper thumbnail of The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity

Journal of Cell Biology, 2008

Research paper thumbnail of An Osteoblast-dependent Mechanism Contributes to the Leptin Regulation of Insulin Secretion

Annals of The New York Academy of Sciences, 2009

Our work focuses on genetic and molecular mechanisms for the reciprocal regulation of bone and en... more Our work focuses on genetic and molecular mechanisms for the reciprocal regulation of bone and energy metabolism orchestrated by leptin and osteocalcin. In the context of this reciprocal regulation, the finding that leptin inhibits insulin secretion by β cells while osteocalcin favors it is surprising. In exploring the molecular bases of this paradox we found that leptin, as is the case for most of its functions, uses a neuronal relay to inhibit insulin secretion. Cell-specific gene-deletion experiments revealed that a component of this neuronal regulation is the sympathetic innervation to osteoblasts. Under the control of leptin the sympathetic tone favors expression in osteoblasts of Esp, which inhibits the metabolic activity of osteocalcin. We further identify ATF4 as a transcription factor that regulates Esp expression and thereby insulin secretion and sensitivity. Taken together these data illustrate the tight connections between bone remodeling and energy metabolism and add further credence to the notion that the osteoblast is a bona fide endocrine cell type.

Research paper thumbnail of Patients with high bone mass phenotype due to Lrp5-T253i mutation have low plasma levels of serotonin

Bone, 2010

The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to a... more The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex-and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean AE SEM: 2.16 AE 0.28 ng/mL versus 3.51 AE 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. ß

Research paper thumbnail of Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

Journal of Bone and Mineral Research, 2010

The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to a... more The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex-and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean AE SEM: 2.16 AE 0.28 ng/mL versus 3.51 AE 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. ß

Research paper thumbnail of Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

Journal of Bone and Mineral Research, 2010

The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to a... more The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex- and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean ± SEM: 2.16 ± 0.28 ng/mL versus 3.51 ± 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. © 2010 American Society for Bone and Mineral Research.

Research paper thumbnail of Divergent multiple carpometacarpal fracture dislocation

Journal of Orthopaedics and Traumatology, 2002

Multiple divergent dislocations of carpometacarpal joints are uncommon injuries. The Authors desc... more Multiple divergent dislocations of carpometacarpal joints are uncommon injuries. The Authors describe a heretofore unreported mediolateral divergence between the fourth and fifth rays coexisting with carpometacarpal dislocation that was reduced and retained by closed technique.

Research paper thumbnail of Unusual K-wire migration

Indian Journal of Pediatrics, 2006

The authors report a case of intra-abdominal migration of a Kirschner wire from the left hip to t... more The authors report a case of intra-abdominal migration of a Kirschner wire from the left hip to the right lobe of the liver in a 5-year-old child. The wire was used for stabilization of the left hip after open reduction for neglected unreduced congenital dislocation of the left hip. The migrated wire was removed by laparotomy. Surprisingly, no injury was noted to any intervening abdominal structure intra-operatively. This unusual migration of a Kirschner wire into a child’s liver has not been reported previously.