The trajectory of IGF‐1 across age and duration of type 1 diabetes

Palta, Mari; LeCaire, Tamara; Sadek-Badawi, Mona; Herrera, Víctor M.; Danielson, Kirstie K.

doi:10.1002/dmrr.2554

Cited by 35 publications

(32 citation statements)

References 44 publications

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“…IR signaling deficiency in osteoblasts is likely relevant to both types of diabetes as emerging evidence supports insulin resistance in osteoblasts in type II diabetes models [78,79]. In addition to low systemic insulin, type I diabetes is associated with decreased serum insulin-like growth factor-1 (IGF1) in both humans and rodent models [80,81]. As IGF1 signals through the IGF1 receptor (IGF1R) to directly stimulate osteoblast differentiation, matrix production and mineralization, IGF1 deficiency likely contributes to the bone formation deficit in diabetes [82–84].…”

Section: Clinical Relevancementioning

confidence: 99%

Glucose metabolism in bone

Karner

Long

2018

Bone

121

110

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The adult human skeleton is a multifunctional organ undergoing constant remodeling through the opposing activities of the bone-resorbing osteoclast and the bone-forming osteoblast. The exquisite balance between bone resorption and bone formation is responsible for bone homeostasis in healthy adults. However, evidence has emerged that such a balance is likely disrupted in diabetes where systemic glucose metabolism is dysregulated, resulting in increased bone frailty and osteoporotic fractures. These findings therefore underscore the significance of understanding the role and regulation of glucose metabolism in bone under both normal and pathological conditions. Recent studies have shed new light on the metabolic plasticity and the critical functions of glucose metabolism during osteoclast and osteoblast differentiation. Moreover, these studies have begun to identify intersections between glucose metabolism and the growth factors and transcription factors previously known to regulate osteoblasts and osteoclasts. Here we summarize the current knowledge in the nascent field, and suggest that a fundamental understanding of glucose metabolic pathways in the critical bone cell types may open new avenues for developing novel bone therapeutics.

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Section: Clinical Relevancementioning

confidence: 99%

Glucose metabolism in bone

Karner

Long

2018

Bone

121

110

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“…C-peptide will be lost at the same time as insulin, since they are both part of the same precursor peptide. Theimportance of the loss of C-peptide and insulin toward the development of the complications of diabetes was supported by more recent experiments showing diabetic animals had a reduced ability to up regulate neurotrophic factors (IGF-1, IGF-1 receptor, p75, and TrkA) in response to nerve crush injury, ultimately leading to reduced regenerative ability and decreased nerve fiber density[190, 196]. This deficiency was largely selective for type I, not type II, diabetic models, suggesting that the deficiency of insulin and C-peptide, not hyperglycemia, leads to axonopathy and decreased nerve fiber density [196].…”

Section: Mechanisms Of Peripheral Neuropathymentioning

confidence: 99%

“…Additional work has clarified the protective role of the insulin induced neurotrophic factor insulin-like growth factor 1 (IGF-1).Given a decrease an insulin, as is seen in type I diabetes, it is perhapsunsurprising that IGF expression is decreased in patients with type I diabetes versus normoglycemic controls [190], Long appreciated for its anti-apoptotic activity in cancer and injury (as reviewed in [256]), IGF-1 was recently found to protect DRG neurons from hyperglycemia induced apoptotic signaling [145]. …”

Section: Mechanisms Of Peripheral Neuropathymentioning

confidence: 99%

Mechanisms of distal axonal degeneration in peripheral neuropathies

Cashman

Höke²

2015

Neuroscience Letters

168

181

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Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration.

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“…T1D is associated with low systemic insulin and insulin like growth factor-1 (IGF-1) levels in humans [14], whereas diminished gene expression of IGF-1, IGF-1 receptor (IGF-1R) and insulin receptor (IR) in bone marrow stromal cells (BMSCs) and low protein levels of IGF-1 and IGF-1R have been observed in STZ-induced diabetic rats [15]. IGF-1 is fundamental for growth and maturation of OBs; it has been shown to stimulate growth and differentiation of OBs from mesenchymal stem cells both in vivo and in vitro [16, 17] and it is essential for bone mineralization [18, 19].…”

Section: Effects Of Type 1 Diabetes On Osteoblastsmentioning

confidence: 99%

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts

Kalaitzoglou

Popescu

Bunn

et al. 2016

Curr Osteoporos Rep

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Purpose of review To describe the effects of Type 1 diabetes on bone cells. Recent findings Type 1 diabetes (T1D) is associated with low bone mineral density, increased risk of fractures and poor fracture healing. Its effects on the skeleton were primarily attributed to impaired bone formation, but recent data suggests that bone remodeling and resorption are also compromised. The hyperglycemic and inflammatory environment associated with T1D impacts osteoblasts, osteocytes and osteoclasts. The mechanisms involved are complex; insulinopenia, pro-inflammatory cytokine production and alterations in gene expression are a few of the contributing factors leading to poor osteoblast activity and survival and, therefore, poor bone formation. In addition, the observed sclerostin level increase accompanied by decreased osteocyte number and enhanced osteoclast activity in T1D results in uncoupling of bone remodeling. Summary T1D negatively impacts osteoblasts and osteocytes whereas its effects on osteoclasts are not well characterized, although the limited studies available indicate increased osteoclast activity, favoring bone resorption.

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The trajectory of IGF‐1 across age and duration of type 1 diabetes

Cited by 35 publications

References 44 publications

Glucose metabolism in bone

Glucose metabolism in bone

Mechanisms of distal axonal degeneration in peripheral neuropathies

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts

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