Somatomedin in Insulin-Dependent Diabetes Mellitus

Cohen, Morrel H.; Jasti, Krishna; Rye, D L

doi:10.1210/jcem-45-2-236

Cited by 46 publications

(16 citation statements)

References 11 publications

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“…Subsequently, Merimee et al (1) found that IGF-I levels in adult diabetic patients with rapidly progressive retinopathy were twice those in patients without retinopathy, patients with less severe retinopathy, or nondiabetic control subjects. However, our study and numerous other studies found no relationship between IGF-I and PDR (3,20,21). Several factors may account for these apparently discrepant results.…”

Section: Discussioncontrasting

confidence: 98%

Is Insulinlike Growth Factor I Associated With Diabetic Retinopathy?

Dills

Moss²,

Klein³

et al. 1990

Diabetes

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Insulinlike growth factor I (IGF-I) is the mediator of the growth-promoting effects of growth hormone and has been suspected of playing a role in the pathogenesis of proliferative diabetic retinopathy (PDR). However, previous attempts to correlate IGF-I levels with PDR have yielded conflicting results. We determined IGF-I levels in a large population-based study of 682 early-onset (diagnosed before 30 yr of age) adult (greater than or equal to 18 yr old) insulin-taking diabetic subjects. PDR was found in 25% of the population. IGF-I levels were measured by radioimmunoassay. The mean serum level of IGF-I was 277 +/- 108 micrograms/L (mean +/- SD). Spearman rank correlations showed statistically significant negative correlations between IGF-I levels and age (r = -0.51, P less than 0.0001), duration of disease (r = -0.36, P less than 0.0001), and glycosylated hemoglobin (r = -0.09, P less than 0.05). There was a significant trend (P less than 0.001) toward decreasing risk of PDR with increasing IGF-I. However, after controlling for duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, and the presence of proteinuria and/or creatinine greater than or equal to 265 microM in a multiple logistic regression model, IGF-I was not significantly associated with PDR. These data suggest that IGF-I may not be a risk factor for the development of PDR.

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Section: Discussioncontrasting

confidence: 98%

Is Insulinlike Growth Factor I Associated With Diabetic Retinopathy?

Dills

Moss²,

Klein³

et al. 1990

Diabetes

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“…This probably accounts for the low levels of circulating IGF-I characteristically seen in diabetes mellitus and the failure of longitudinal growth that results when metabolic control is poor (14)(15)(16)(17)(18)(19). It is not clear what component of the diabetic metabolic disturbance induces reductions in IGF-I gene expression, synthesis, and secretion, but a similar outcome in other states of nutrient deprivation (including starvation and protein/energy restriction) suggest that nutrient supply or insulin itself may be responsible, rather than the level of glycemia (10-13, 17, 18).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, poorly controlled human IDDM and insulinopenic diabetes mellitus in the rat are associated with reduced circulating IGF-I levels, which may account for growth failure (14)(15)(16)(17)(18). Decreased serum IGF-I levels are thought to result primarily from decreased IGF-I synthesis in liver and those extrahepatic sites in which it has been studied (18,19).…”

mentioning

confidence: 99%

Pituitary Insulin-Like Growth Factor-I Content and Gene Expression in the Streptozotocin-Diabetic Rat: Evidence for Tissue-Specific Regulation*

et al. 1991

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Insulinopenic diabetes mellitus in the rat is associated with reduced circulating levels of insulin-like growth factor-I (IGF-I), resulting primarily from decreased IGF-I synthesis in liver and extrahepatic sites. Plasma GH levels in these animals are also suppressed, with loss of episodic secretion and decreased pituitary synthesis. Intrapituitary IGF-I has been postulated to exert local autocrine/paracrine negative feedback regulation on GH synthesis and secretion. The present studies were designed to examine regulation of pituitary IGF-I peptide content and gene expression in insulinopenic streptozotocin (STZ)-diabetic rats compared to that in liver and testis. Serum IGF-I levels were reduced by 86% in STZ-diabetic rats together with reduction of IGF-I content in liver (53%) and testis (74%; all P less than 0.001 vs. control). Concomitantly, liver and testicular IGF-I mRNA levels were reduced by 90% (P less than 0.001 vs. control). Insulin treatment restored IGF-I peptide levels in serum, liver, and testis toward normal, with a partial but significant increase in liver IGF-I mRNA. In contrast, pituitary IFG-I peptide content increased by 69% in STZ-diabetic rats (P less than 0.001 vs. control), with no change in IGF-I gene expression. Insulin treatment completely reversed the rise of pituitary IGF-I peptide content. These results demonstrate a novel discordance in the regulation of IGF-I gene expression and peptide content between pituitary and other tissues in STZ-induced diabetic rats. Elevated IGF-I levels in the pituitaries of these animals may partly explain the suppressed GH synthesis and secretion seen in STZ-diabetic rats and provide further evidence for a potential autocrine or paracrine role of pituitary IGF-I in GH regulation.

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“…In some human diabetic subjects serum IGF-I levels are not reduced (24)(25)(26) and in others they may even be elevated (27)(28)(29). Furthermore, Schalch et al (30) found no effect of insulin on Sm-C secretion in a perfused rat liver system, and Scott and Baxter (11) reported that although insulin treatment of diabetic rats restored their serum Sm-C levels and the capacity oftheir hepatocytes to secrete the IGF in vitro, it failed to stimulate Sm-C secretion by hepatocytes of the diabetic rats in vitro when added to the incubation medium.…”

Section: Introductionmentioning

confidence: 99%

Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

Griffen

Russell

Katz

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver has not been established. Previous studies indicated that insulin does not acutely regulate glucose metabolism by a direct hepatic effect. More recent observations suggest that the role of insulin in regulating body growth may be mediated, at least in part, by the liver. Our experiments were designed to test whether insulin can promote body growth and regulate glucose metabolism by a direct hepatic action in vivo. Rats were made diabetic by injections of streptozotocin, and insulin or solvent was infused into the jugular vein (JV) or the hepatic portal vein (HPV) for 14 days using catheters that were attached to osmotic minipumps. Infusion of a low dose of insulin (2 units per kg per day) into the JV had no effects on the hyperglycemia, body weight gain, tail growth, tibial epiphysial cartilage plate thickness, or serum levels of somatomedin C in the diabetic rats. However, the same dose given into the HPV caused a 30% reduction of blood glucose and stimulated a significant degree of growth, as determined by all indices. Infusion of a higher dose of insulin (5 units per kg per day) into either vein caused full restoration of body weight gain and tail growth and it restored the glycemic status almost to normal. However, it did not increase the tibial epiphysial plate width or serum somatomedin C levels above those of the rats given the low dose of the hormone into the HPV. These results indicate that insulin can act directly on the liver to promote body growth and to regulate glucose metabolism. The significance of direct delivery of insulin from the pancreatic beta cells to the liver may be as much for growth control as for glucose homeostasis.

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Somatomedin in Insulin-Dependent Diabetes Mellitus

Cited by 46 publications

References 11 publications

Is Insulinlike Growth Factor I Associated With Diabetic Retinopathy?

Is Insulinlike Growth Factor I Associated With Diabetic Retinopathy?

Pituitary Insulin-Like Growth Factor-I Content and Gene Expression in the Streptozotocin-Diabetic Rat: Evidence for Tissue-Specific Regulation*

Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

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