Effects of Diabetes and Insulin on Bone Physiology

Verhaeghe, Johan; Bouillon, Roger

doi:10.1016/b978-0-12-373884-4.00003-3

Cited by 3 publications

(2 citation statements)

References 130 publications

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“…The relationship between BMD and insulin levels has also been reported in human type 2 diabetics, where BMD was positively correlated with fasting serum insulin concentrations (Rishaug et al 1995). Furthermore, the increased BMDs at various skeletal sites have been reported in hyperinsulinemic individuals in the presence and absence of type 2 diabetes (Verhaege & Bouillon 1996). Taken together, these studies suggest that hyperinsulinemia contributes to increased BMD in both humans and rodents.…”

Section: Hyperinsulinemia and Skeletal Tissuesupporting

confidence: 65%

Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat

Prisby¹,

Swift²,

Bloomfield³

et al. 2008

Journal of Endocrinology

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Osteopenia and an enhanced risk of fracture often accompany type 1 diabetes. However, the association between type 2 diabetes and bone mass has been ambiguous with reports of enhanced, reduced, or similar bone mineral densities (BMDs) when compared with healthy individuals. Recently, studies have also associated type 2 diabetes with increased fracture risk even in the presence of higher BMDs. To determine the temporal relationship between type 2 diabetes and bone remodeling structural and mechanical properties at various bone sites were analyzed during pre-diabetes (7 weeks), shortterm (13 weeks), and long-term (20 weeks) type 2 diabetes. BMDs and bone strength were measured in the femora and tibiae of Zucker diabetic fatty rats, a model of human type 2 diabetes. Increased BMDs (9-10%) were observed in the distal femora, proximal tibiae, and tibial mid-shafts in the pre-diabetic condition that corresponded with higher plasma insulin levels. During short-and long-term type 2 diabetes, various parameters of bone strength and BMDs were lower (9-26%) in the femoral neck, distal femora, proximal tibiae, and femoral and tibial mid-shafts. Correspondingly, blood glucose levels increased by 125% and 153% during short-and longterm diabetes respectively. These data indicate that alterations in BMDs and bone mechanical properties are closely associated with the onset of hyperinsulinemia and hyperglycemia, which may have direct adverse effects on skeletal tissue. Consequently, disparities in the human literature regarding the effects of type 2 diabetes on skeletal properties may be associated with the bone sites studied and the severity or duration of the disease in the patient population studied.

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Section: Hyperinsulinemia and Skeletal Tissuesupporting

confidence: 65%

Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat

Prisby¹,

Swift²,

Bloomfield³

et al. 2008

Journal of Endocrinology

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show abstract

“…Both insulin and IGF1 are known to induce a wide variety of growth and metabolic responses and play essential roles in anabolic regulation of bone metabolism [43] . Several genes involved in the insulin and IGF1 pathway were identified to be associated with the FL traits in this study.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study Identifies Loci for Body Composition and Structural Soundness Traits in Pigs

et al. 2011

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BackgroundThe recent completion of the swine genome sequencing project and development of a high density porcine SNP array has made genome-wide association (GWA) studies feasible in pigs.Methodology/Principal FindingsUsing Illumina's PorcineSNP60 BeadChip, we performed a pilot GWA study in 820 commercial female pigs phenotyped for backfat, loin muscle area, body conformation in addition to feet and leg (FL) structural soundness traits. A total of 51,385 SNPs were jointly fitted using Bayesian techniques as random effects in a mixture model that assumed a known large proportion (99.5%) of SNPs had zero effect. SNP annotations were implemented through the Sus scrofa Build 9 available from pig Ensembl. We discovered a number of candidate chromosomal regions, and some of them corresponded to QTL regions previously reported. We not only have identified some well-known candidate genes for the traits of interest, such as MC4R (for backfat) and IGF2 (for loin muscle area), but also obtained novel promising genes, including CHCHD3 (for backfat), BMP2 (for loin muscle area, body size and several FL structure traits), and some HOXA family genes (for overall leg action). The candidate regions responsible for body conformation and FL structure soundness did not overlap greatly which implied that these traits were controlled by different genes. Functional clustering analyses classified the genes into categories related to bone and cartilage development, muscle growth and development or the insulin pathway suggesting the traits are regulated by common pathways or gene networks that exert roles at different spatial and temporal stages.Conclusions/SignificanceThis study is one of the earliest GWA reports on important quantitative traits in pigs, and the findings will contribute to the further biological function analysis of the identified candidate genes and potential utilization of them in marker assisted selection.

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Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

et al. 2023

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Type 1 diabetes mellitus (T1DM) is the most common autoimmune chronic disease in young patients. It is caused by the destruction of pancreatic endocrine β-cells that produce insulin in specific areas of the pancreas, known as islets of Langerhans. As a result, the body becomes insulin deficient and hyperglycemic. Complications associated with diabetes are life-threatening and the current standard of care for T1DM consists still of insulin injections. Lifesaving, exogenous insulin replacement is a chronic and costly burden of care for diabetic patients. Alternative therapeutic options have been the focus in these fields. Advances in molecular biology technologies and in microfabrication have enabled promising new therapeutic options. For example, islet transplantation has emerged as an effective treatment to restore the normal regulation of blood glucose in patients with T1DM. However, this technique has been hampered by obstacles, such as limited islet availability, extensive islet apoptosis, and poor islet vascular engraftment. Many of these unsolved issues need to be addressed before a potential cure for T1DM can be a possibility. New technologies like organ-on-a-chip platforms (OoC), multiplexed assessment tools and emergent stem cell approaches promise to enhance therapeutic outcomes. This review will introduce the disorder of type 1 diabetes mellitus, an overview of advances and challenges in the areas of microfluidic devices, monitoring tools, and prominent use of stem cells, and how they can be linked together to create a viable model for the T1DM treatment. Microfluidic devices like OoC platforms can establish a crucial platform for pathophysiological and pharmacological studies as they recreate the pancreatic environment. Stem cell use opens the possibility to hypothetically generate a limitless number of functional pancreatic cells. Additionally, the integration of stem cells into OoC models may allow personalized or patient-specific therapies.

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Effects of Diabetes and Insulin on Bone Physiology

Cited by 3 publications

References 130 publications

Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat

Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat

Genome-Wide Association Study Identifies Loci for Body Composition and Structural Soundness Traits in Pigs

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

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