An Insulinlike Growth Factor I-Resistant State in Cartilage of Diabetic Rats Is Ameliorated by Hypophysectomy: Possible Role of Metabolism

Kelley, Kevin M.; Russell, Sharon M.; Matteucci, Mark L; Nicoll, C S

doi:10.2337/diab.42.3.463

Cited by 16 publications

(4 citation statements)

References 40 publications

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“…Therefore, it appears that activation of the adrenocorticotropic hormone (ACTH)-adrenal cortical axis contributes to the GH resistance in rats with IDDM. This conclusion is supported by observations that euglycemia and responsiveness to GH and IGF-I are partially restored when animals with IDDM are hypophysectomized or adrenalectomized (4,(7)(8)(9)(10).…”

mentioning

confidence: 65%

“…Therefore, the failure of reduced IGF-I to cause a decrease in TEPW in the Ax nondiabetic rats (Table 1) is presumably due to the absence of corticosterone. Cartilage growth and responsiveness to GH in vivo and to IGF-I in vitro are compromised in animals with IDDM (4,7). This effect is reflected in reduced linear skeletal growth and TEPW (41).…”

Section: Stzmentioning

confidence: 99%

“…Diabetes 44:1420-1425, 1995 C irculating levels of insulin-like growth factor (IGF) I and growth are often reduced in humans and animals with insulin-dependent diabetes mellitus (IDDM). Insulin deficiency, hepatic resistance to growth hormone (GH), and resistance of peripheral tissues to the anabolic actions of IGF-I are partially responsible for these deficits (1)(2)(3)(4). Previous studies suggest that elevated adrenal corticosterone production is partly responsible for these abnormalities (5).…”

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confidence: 99%

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Corticosterone Regulation of Insulin-Like Growth Factor I, IGF-Binding Proteins, and Growth in Streptozotocin-Induced Diabetic Rats

Rodgers

Strack²,

Dallman³

et al. 1995

Diabetes

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The experiments reported herein were conducted to determine how corticosterone regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced diabetic rats. Males were bilaterally adrenalectomized (Ax) or sham Ax and given intravenous injections of 0, 30, or 65 mg STZ per kg body wt (0, 30, or 65 STZ) to induce varying degrees of insulin deficiency and implanted with 100-mg pellets containing 0, 40, or 80% corticosterone in cholesterol. Changes in plasma IGFBP concentrations were determined by Western ligand blotting or immunoblots. Neither IGFBP-5 nor IG-FBP-6 was detected in any of the treatment groups. Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed. Adrenalectomy had no affect on tibial growth or plasma IGFBP-1 in these animals. Plasma IGF-I, IGFBP-1 and -3, and tibial growth were equal among 0, 30, and 65 STZ Ax rats that did not receive corticosterone. Plasma IGFBP-4 was inversely related to the amount of STZ injected in these animals, and IGFBP-2 was elevated in those given the high dose of STZ. In the 0 STZ Ax rats, plasma IGF-I and IGFBP-3 increased in proportion to the corticosterone implant dose, but IGFBP-1 was unaffected. By contrast, IGF-I and IGFBP-3 were unaltered by corticosterone in the 30 STZ Ax rats, and IGFBP-1 increased in proportion with the dose of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

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confidence: 65%

Section: Stzmentioning

confidence: 99%

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confidence: 99%

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Corticosterone Regulation of Insulin-Like Growth Factor I, IGF-Binding Proteins, and Growth in Streptozotocin-Induced Diabetic Rats

Rodgers

Strack²,

Dallman³

et al. 1995

Diabetes

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“…38,39 In the streptozotocin-induced diabetic rat model, researchers have demonstrated decreased proteoglycan and type 2 collagen content as well as cartilage resistance to the anabolic effects of insulin-like growth factor (IGF)-I. 40,41 Furthermore, fibrochrondrocytes in meniscal tissue have the ability to regenerate in the presence of IGF-1. 42 Given that patients with diabetes may have decreased IGF-1 levels 43 and therefore diminished regenerative capacity for meniscal tissue, these patients may be more susceptible to meniscal degeneration.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Association of Metabolic Biomarkers With Knee Cartilage Composition and Structural Abnormalities Using MRI: A Pilot Study

et al. 2020

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Objective The goal of this study was to explore the metabolic syndrome–associated phenotype of osteoarthritis by investigating the cross-sectional associations of glycemic markers and serum lipids with knee cartilage composition and structural abnormalities in middle-aged adults. Design Twenty participants between 40 to 70 years of age with Kellgren-Lawrence score 0-1 in at least one knee were recruited at a single center. Knee cartilage composition was assessed using 3.0 T cartilage T2 and T1ρ mapping. Evaluation of structural knee abnormalities was performed using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression was used to assess the associations of standardized fasting glucose (FG), hemoglobin A1c (HbA1c), insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL cholesterol, and triglycerides with cartilage T2 and T1ρ as well as WORMS subscores, adjusting for body mass index. Results Higher FG and higher HbA1c were associated with higher WORMS meniscus sum (beta coefficient 1.31 [95% confidence interval (CI): 0.57, 2.05], P = 0.002 per standard deviation [SD] increase in FG; beta coefficient 0.90 [95% CI: 0.07, 1.73], P = 0.035 per SD increase in HbA1c). Also, higher total cholesterol and higher non-HDL cholesterol were associated with higher WORMS cartilage sum (beta coefficient 0.94 [95% CI: 0.01, 1.86], P = 0.048 per SD increase in total cholesterol; beta coefficient 1.05 [95% CI: 0.14, 1.96], P = 0.03 per SD increase in non-HDL cholesterol). Conclusions Higher FG and HbA1c were associated with increased meniscal degeneration while higher total and non-HDL cholesterol were associated with increased cartilage degeneration.

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Down-regulation in the insulin-like growth factor (IGF) axis during hibernation in the golden-mantled ground squirrel,Spermophilus lateralis: IGF-I and the IGF-binding proteins (IGFBPs)

Schmidt

Kelley

2001

J. Exp. Zool.

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The golden‐mantled ground squirrel, Spermophilus lateralis, undergoes a profound winter hibernation that represents, among other changes, a prolonged period of starvation. In addition to dramatic metabolic and other physiological adaptations during hibernation which serve to reduce fuel energy expenditure, we have hypothesized that there may also be significant changes in the endocrine axis that regulates energetically‐expensive somatic growth. As compared with euthermic, non‐hibernating controls, hibernating S. lateralis were found to have 75%‐reduced serum concentrations of insulin‐like growth factor‐I (IGF‐I; from ∼625 to ∼150 ng/ml in both females and males, P < 0.05). While IGFBP‐3 was the predominant IGFBP in serum of the euthermic controls, its levels were reduced to a similar degree in serum from the hibernating animals. IGFBP‐4 was present at relatively low levels in the euthermic controls, and was reduced to undetectable levels in hibernating animals. Surprisingly, there was no IGFBP detectable in the 30 kDa range in either euthermic or hibernating S. lateralis, suggesting that IGFBP‐1 does not play a role in hibernation‐related changes in the IGF axis. In accordance with these endocrine changes, when serum from hibernating S. lateralis was added to cartilage explant cultures (at a 5% v/v concentration), it exhibited no ability to alter 35S‐proteoglycan synthetic rate, whereas serum from the euthermic squirrels significantly stimulated synthetic activity by 2‐fold. These results suggest that part of hibernation adaptation in S. lateralis includes down‐regulation in the growth‐regulatory IGF axis. J. Exp. Zool. 289:66–73, 2001. © 2001 Wiley‐Liss, Inc.

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An Insulinlike Growth Factor I-Resistant State in Cartilage of Diabetic Rats Is Ameliorated by Hypophysectomy: Possible Role of Metabolism

Cited by 16 publications

References 40 publications

Corticosterone Regulation of Insulin-Like Growth Factor I, IGF-Binding Proteins, and Growth in Streptozotocin-Induced Diabetic Rats

Corticosterone Regulation of Insulin-Like Growth Factor I, IGF-Binding Proteins, and Growth in Streptozotocin-Induced Diabetic Rats

Investigating the Association of Metabolic Biomarkers With Knee Cartilage Composition and Structural Abnormalities Using MRI: A Pilot Study

Down-regulation in the insulin-like growth factor (IGF) axis during hibernation in the golden-mantled ground squirrel,Spermophilus lateralis: IGF-I and the IGF-binding proteins (IGFBPs)

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