Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice
The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated...
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| Published in | Bone (New York, N.Y.) Vol. 50; no. 2; pp. 568 - 575 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.02.2012
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes.
This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.
► Daily injections of osteocalcin increase β-cell mass and insulin secretion. ► Daily injections of osteocalcin improve insulin sensitivity in a mouse model of type 2 diabetes. ► Daily injections of osteocalcin prevent obesity by increasing energy expenditure. ► Daily injections of osteocalcin prevent liver steatosis. |
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| AbstractList | The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes.The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes. The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both beta -cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes. This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism. The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes. The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes. This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism. ► Daily injections of osteocalcin increase β-cell mass and insulin secretion. ► Daily injections of osteocalcin improve insulin sensitivity in a mouse model of type 2 diabetes. ► Daily injections of osteocalcin prevent obesity by increasing energy expenditure. ► Daily injections of osteocalcin prevent liver steatosis. Abstract The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes. This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism. |
| Author | Ferron, Mathieu Karsenty, Gérard Levine, Robert L. Ducy, Patricia McKee, Marc D. |
| AuthorAffiliation | 3 Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 1 Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 2 Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada |
| AuthorAffiliation_xml | – name: 1 Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA – name: 2 Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada – name: 3 Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA |
| Author_xml | – sequence: 1 givenname: Mathieu surname: Ferron fullname: Ferron, Mathieu organization: Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA – sequence: 2 givenname: Marc D. surname: McKee fullname: McKee, Marc D. organization: Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada – sequence: 3 givenname: Robert L. surname: Levine fullname: Levine, Robert L. organization: Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA – sequence: 4 givenname: Patricia surname: Ducy fullname: Ducy, Patricia email: pd2193@columbia.edu organization: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA – sequence: 5 givenname: Gérard surname: Karsenty fullname: Karsenty, Gérard email: gk2172@columbia.edu organization: Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21550430$$D View this record in MEDLINE/PubMed |
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| Keywords | Energy expenditure Osteocalcin Glucose Insulin Liver steatosis |
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| Snippet | The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a... Abstract The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy... |
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| SubjectTerms | Animals Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - prevention & control Diet, High-Fat Energy expenditure Energy Metabolism - drug effects Fatty Liver - complications Fatty Liver - pathology Fatty Liver - prevention & control Glucose Glucose - metabolism Glucose Tolerance Test Injections, Intraperitoneal Insulin Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology Liver steatosis Mice Mice, Inbred C57BL Mitochondria - drug effects Mitochondria - metabolism Motor Activity - drug effects Obesity - complications Obesity - prevention & control Orthopedics Osteocalcin Osteocalcin - administration & dosage Osteocalcin - pharmacology Osteocalcin - therapeutic use |
| Title | Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice |
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