About
Titles
Ensign Professor Emeritus of Medicine (Endocrinology)
Director, Yale Bone Center; Member, Medical Oncology; Attending Physician, Internal Medicine; Associate Director, Yale Center for X-Linked Hypophosphatemia, EndocrinologyBiography
Dr. Karl Insogna is a tenured Professor at Yale and an internationally recognized expert in the field of metabolic bone disease. He has published widely on the topic in the field's leading scientific journals, is quoted often in the lay press, and has frequently appeared on radio and television. He is a Fellow of the American Association for the Advancement of Science, and was a member of the National Institutes of Health Consensus Conference, which established new recommendations for the optimal level of calcium intake for all Americans - now adopted nationwide. He is a leading researcher in the causes of bone loss in such diseases as osteoporosis and primary hyperparathyroidism, and is currently conducting studies in, among other areas, the role of diet in the development of osteoporosis.
Appointments
Endocrinology
EmeritusPrimaryEndocrinology
Senior Research ScientistSecondary
Other Departments & Organizations
- Bone Center
- Cancer Signaling Networks
- Center for X-Linked Hypophosphatemia, Yale
- Dean's Workshops
- Diabetes Research Center
- Discovery to Cure Internship
- Endocrinology
- Fellowship Training
- Insogna Lab
- Internal Medicine
- WHRY Pilot Project Program Investigators
- Women's Health Research at Yale
- Yale Cancer Center
- Yale Ventures
Education & Training
- Chief Resident
- University of Rochester (1980)
- Residency
- University of Rochester (1979)
- MD
- University of Connecticut (1976)
Board Certifications
Endocrinology Diabetes & Metabolism
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1983
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1979
Research
Overview
Dr. Insogna maintains active programs in both clinical and bench research.
In the clinical arena, Dr. Insogna is interested in the role of dietary protein in skeletal metabolism. Over the past decade, he and Dr. Jane Kerstetter from the University of Connecticut have established a new paradigm for the effect of dietary protein on calcium homeostasis. They have found that, contrary to the widely held view, increases in dietary protein within the physiologic range do not result in negative bone balance. Using dual stable calcium isotopes, they determined that the long-recognized hypercalciuria, which attends an increase in dietary protein, is quantitatively explained by improved intestinal calcium absorption, rather than increased bone resorption. In fact, the rate of resorption tends to slow as dietary protein is increased from low to high-normal. These data have led Drs. Insogna, Kerstetter, and Anne Kenney (from the University of Connecticut) to launch an NIH-funded, multi-center trial examining the impact of a dietary protein supplement on bone metabolism in postmenopausal women. Ongoing studies also seek to better define the cellular and molecular mechanisms by which dietary protein augments intestinal calcium absorption. Some of this work suggests a potential role for the calcium-sensing receptor, but alternative theories are currently being explored in the laboratory.
Another area of active clinical investigation involves understanding the factors that lead to skeletal disease in adult patients with X-linked hypophosphatemic rickets. Research over the last decade has improved our understanding of the pathogenesis of hypophosphatemic disorders, and this new information is being applied in two clinical trials currently being conducted by Dr. Insogna and Dr. Thomas Carpenter from the Department of Pediatrics. These studies seek to determine the clinical and biochemical factors that lead to skeletal complications, such as enthesopathy and spinal ligament calcification, in this disease. Finally, Dr. Insogna and Dr. M. Tish Knobf from the School of Nursing are beginning an NIH-funded study to examine the impact of exercise on bone health in postmenopausal breast cancer survivors.
In the laboratory, Dr. Insogna’s interest focuses on cellular mechanisms of PTH-induced bone resorption and bone anabolism. He has had a long-standing interest in the role of interleukin-6 in mediating PTH-induced bone resorption. Current efforts in that area focus on the role of IL-6 in PTH-induced RANK ligand expression. Another major research effort in the laboratory is to define the role of the two Colony Stimulating Factor-1 (CSF1) isoforms in bone. Work from the Insogna laboratory has established that CSF1 is the major colony-stimulating factor released by osteoblasts in response to PTH. Further work supports the hypothesis that the soluble and membrane CSF1 isoforms serve non-redundant roles in bone. Selective deletion of each isoform in vivo is being pursued to better define their separate roles. As an example, we are currently examining the possibility that sCSF-1 has a unique role in estrogen-deficiency bone loss.
The laboratory is also interested in the effects of CSF1 in mature osteoclasts. CSF-1 is an important chemoattractant in vivo for osteoclasts, and the laboratory is exploring the molecular mechanisms by which CSF-1 induces cytoskeletal remodeling and osteoclast motility. The downstream targets for CSF1 in osteoclasts include PI 3-kinase, Rac1, LIM kinase 1, and cofilin. In the course of this work, the laboratory has identified unique interacting proteins that partner with Rac1, including BCA3, (Breast Cancer Associated Protein 3). The role of BCA3 is incompletely understood but one function appears to be a nuclear/cytoplasmic shuttle. This finding, in conjunction with an emerging nuclear role Rac1 suggests novel, hitherto unappreciated nuclear functions for Rac1 in osteoclasts. There is an ongoing interest in the laboratory in identifying environmental and genetic modifiers of PTH’s anabolic actions, which has lead to studies exploring the modulating effects of aging, diet and genes that regulate osteoclast function. Finally, the laboratory is interested in Wnt signaling and its role in lineage allocation in bone. Our current interest is in identifying Wnt-dependent metabolic pathways that regulate mesenchymal stem cell differentiation towards the osteoblast lineage and away from an adipocyte fate. For more information on Dr. Insogna's bench and clinical research, please visit https://medicine.yale.edu/lab/insogna.
Medical Subject Headings (MeSH)
Academic Achievements and Community Involvement
Links & Media
News
- April 03, 2024Source: Well+Good
The Easiest Ways To Eat More Vitamin D in the Wintertime, From Bone Density Doctors and RDs
- September 29, 2023
“Complete Academic Physician” Dr. Karl Insogna Retires From Clinical Duties
- March 16, 2023
Discoveries & Impact (March 2023)
- October 17, 2022
Yale Endocrinology Presents Studies on Type 2 Diabetes, Obesity and Breast Cancer