Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy

Picke, Ann-Kristin; Alaguero, I. Gordaliza; Campbell, Graeme; Glüer, Claus‐C.; Salbach-Hirsch, Juliane; Rauner, Martina; Hofbauer, Lorenz C.; Hofbauer, Christine

doi:10.1016/j.bone.2015.06.001

Cited by 46 publications

(49 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies investigating the effect of insulin treatment on fracture risk are inconsistent. In rats, insulin treatment reversed the negative effects of type 2 diabetes on bone defect regeneration by enhancing osteoblast function and bone formation (110). In men with type 2 diabetes however, increased fracture rate was limited to those treated with insulin (50).…”

Section: Insulinmentioning

confidence: 97%

Complex interplay among adiposity, insulin resistance and bone health

Tonks

Samocha-Bonet

et al. 2018

Clinical Obesity

View full text Add to dashboard Cite

Obesity and osteoporosis are common public health problems. Paradoxically, while obesity is associated with higher bone density, type 2 diabetic obese individuals have an increased fracture risk. Although obesity and insulin resistance co-exist, some obese individuals remain insulin-sensitive. We suggest that the apparent paradox relating obesity, bone density and fracture risk in type 2 diabetes may be at least partly influenced by differences in bone strength and quality between insulin-resistant and insulin-sensitive obese individuals. In this review, we focus on the complex interplay between, adiposity, insulin resistance and osteoporotic fracture risk and suggest that this is an important area of study that has implications for individually tailored and targeted treatment to prevent osteoporotic fracture in obese type 2 diabetic individuals.

show abstract

Section: Insulinmentioning

confidence: 97%

Complex interplay among adiposity, insulin resistance and bone health

Tonks

Samocha-Bonet

et al. 2018

Clinical Obesity

View full text Add to dashboard Cite

show abstract

“…In contrast, neither bone marrow lipid nor the size/number of BMAs is different in distal tibial cBMAT of lean and obese mice (Figure 2). Importantly, overeating of a standard laboratory chow diet also increases rBMAT in rodents with a genetic predisposition for hyperphagia 32, 39, 40 . Thus, it is the positive energy balance and/or development of obesity that contributes to rBMAT expansion, rather than dietary composition.…”

Section: Development and Regulation Of Bmat In Humans And Rodentsmentioning

confidence: 98%

Development, regulation, metabolism and function of bone marrow adipose tissues

Hardij

Bagchi

et al. 2018

Bone

123

128

View full text Add to dashboard Cite

Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells.

show abstract

“…At the cellular level, these abnormalities are associated with impaired endochondral ossification, lower bone formation due to reductions in osteoblast number and activity, and mild osteopetrosis due to impaired osteoclast function (Kishida, et al 2005; Turner, et al 2013). Not surprisingly, bone mechanical properties are often reduced and bone regeneration impaired in leptin signaling-deficient rodents (Hamann, et al 2014; Hamann, et al 2013; Khan, et al 2013; Picke, et al 2015; Wallner, et al 2015). …”

Section: Introductionmentioning

confidence: 99%

Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism

Philbrick

Wong

Branscum

et al. 2017

Journal of Endocrinology

View full text Add to dashboard Cite

Leptin, the protein product of the ob gene, is essential for normal bone growth, maturation, and turnover. Peripheral actions of leptin occur at lower serum levels of the hormone than central actions because entry of leptin into the central nervous system (CNS) is limited due to its saturable transport across the blood brain barrier (BBB). We performed a study in mice to model the impact of leptin production associated with different levels of adiposity on bone formation and compared the response with well-established centrally-mediated actions of the hormone on energy metabolism. Leptin was infused (0, 4, 12, 40, 140, or 400 ng/h) for 12 days into 6-week-old female ob/ob mice (n=8/group) using sc implanted osmotic pumps. Treatment resulted in a dose-associated increase in serum leptin. Bone formation parameters were increased at EC50 infusion rates of 7–17 ng/h whereas higher levels (EC50, 40–80 ng/h) were required to similarly impact indices of energy metabolism. We then analyzed gene expression in tibia and hypothalamus at dose rates of 0, 12 and 140 ng/h; the latter dose resulted in serum leptin levels similar to WT mice. Infusion with 12 ng/h leptin increased expression of genes associated with Jak/Stat signaling and bone formation in tibia with minimal effect on Jak/Stat signaling and neurotransmitters in hypothalamus. The results suggest that leptin acts peripherally to couple bone acquisition to energy availability and that limited transport across the BBB insures that the growth promoting actions of peripheral leptin are not curtailed by the hormone’s CNS-mediated anorexigenic actions.

show abstract

Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy

Cited by 46 publications

References 21 publications

Complex interplay among adiposity, insulin resistance and bone health

Complex interplay among adiposity, insulin resistance and bone health

Development, regulation, metabolism and function of bone marrow adipose tissues

Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism

Contact Info

Product

Resources

About