Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Somatomedins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1985

Nutrition and somatomedin. XIV. Altered levels of somatomedins and somatomedin inhibitors in rats with streptozotocin-induced diabetes.

Diabetes is associated with poor growth despite elevated levels of growth hormone (GH). Skeletal GH effects are mediated by somatomedins; in diabetes, somatomedins measured by radioassay are normal, yet somatomedin activity measured by bioassay is low. Since bioassay measurements reflect the presence of both somatomedins and somatomedin inhibitors, we asked if diabetes might be associated with discordant regulation of these circulating factors. Graded severity of diabetes was induced in rats by injection of streptozotocin at 37, 73, 146, and 293 mg/kg. After two days, metabolic derangement varied from normal serum beta-hydroxybutyrate with slight increase in glucose and minimal weight loss at 37 mg/kg streptozotocin to beta-hydroxybutyrate 10.6 mmol/L, glucose 447 mg/dL, and 33 g weight loss at 293 mg/kg streptozotocin. After fractionation of serum on Sephacryl S-300 pH 7.0, somatomedins and somatomedin inhibitors were measured by rat cartilage bioassay. Somatomedins (Kav 0.25 to 0.50) were comparable to control levels despite beta-hydroxybutyrate 2 mmol/L, glucose 534 mg/dL, and weight loss 11 g at 73 mg/kg streptozotocin and fell only at higher streptozotocin dosage. In contrast, somatomedin inhibitors (Kav 0.62 to 0.88) began to rise at 37 mg/kg streptozotocin and increased with higher dosage. Levels of somatomedins were correlated weakly only with beta-hydroxybutyrate (r = 0.48, P less than 0.05), while somatomedin inhibitors were correlated significantly with all indices, particularly beta-hydroxybutyrate (r = 0.78, P less than 0.0001). The early rise in somatomedin inhibitors but late fall in somatomedins could explain low somatomedin activity (and poor growth) despite normal levels of somatomedins measured by radioassay; measurement of somatomedin inhibitors may provide an index of growth potential in diabetes mellitus.

3-Hydroxybutyric Acid↗
PubMed1989

Nutrition and somatomedin: nutritionally regulated release of somatomedins and somatomedin inhibitors from perfused livers in rats.

Circulating somatomedin activity reflects the presence of both somatomedins and somatomedin inhibitors, factors which antagonize the growth-promoting actions of somatomedins. Although both are regulated by nutrition, somatomedin inhibitors respond more rapidly than somatomedins to refeeding in fasted animals. To explore the role of the liver in such responses, release of somatomedin activity and somatomedin inhibitor activity was assessed during perfusion of livers from normal, fasted, and fasted-refed rats. Size-exclusion high-performance liquid chromatography (HPLC) revealed that liver perfusates contain both somatomedin and somatomedin inhibitor activity of apparent molecular weight (mol wt) comparable to that found in the circulation (approximately 7,000 and approximately 30,000, respectively), as well as activity of apparently higher wt. In subsequent studies, responses to nutrition were evaluated as fluctuations in bioactivity only of mol wt comparable to that found in the circulation. Release of both somatomedin and somatomedin inhibitor activity was progressive over at least two hours of recirculating perfusion. Perfusates of livers from normal fed rats had somatomedin activity (stimulation of cartilage SO4 uptake) 94 +/- 19% above buffer (P less than .01), which fell to undetectable levels after three days of fasting. With refeeding, perfusate somatomedin activity rose within three hours to approximately 25% of levels in fed rats, but did not become significant until after 12 hours (29 +/- 7%, P less than .02). Perfusates of livers of fed rats also contained somatomedin inhibitor activity (42 +/- 10% inhibition of cartilage stimulation by normal serum), which rose after three days of fasting to 114 +/- 22% (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Nutrition and somatomedin--XII. Fractionation of somatomedins and somatomedin inhibitors in normal and diabetic rats.

Bioassayable somatomedins and somatomedin inhibitors were examined after chromatographic separation, using serum from normal rats (enriched in somatomedins) and diabetic rats (enriched in somatomedin inhibitors). At neutral pH, gel filtration on Sephacryl S-300 revealed somatomedins at mol. wt approximately 140,000 (presumably carrier-bound) and inhibitors at mol. wts approximately 250,000, approximately 24,000 and approximately 1,000. At acid pH, gel filtration on Sephadex G-50 revealed somatomedins at mol. wt approximately 8,000 (presumably carrier-free) and a single inhibitor at mol. wt approximately 21,000. Ion exchange chromatography revealed that the inhibitor(s) may be more acidic than the somatomedins, but only low quantities of somatomedins were recovered. Sephadex G-50 fractionation was applied to pathophysiologic models in rats: 3 days of fasting were associated with a 62% fall in somatomedins and a 159% rise in inhibitors; 2 days of diabetes were associated with a 60% fall in somatomedins and a 344% rise in inhibitors. Since chromatography on Sephadex G-50 at pH 2.4 appears to provide adequate separation of somatomedins and somatomedin inhibitors with good estimated recovery of biological activity, this simple approach may be a probe useful in examining the regulation of somatomedins and somatomedin inhibitors in vivo.

Animals↗
PubMed1988

Nutrition and somatomedin. XVI: Somatomedins and somatomedin inhibitors in fasted and refed rats.

Nutritional deprivation is associated with poor growth and decreased levels of net circulating somatomedin activity, as measured by bioassay. Since somatomedin activity reflects the contributions both of somatomedins (which stimulate cartilage) and of somatomedin inhibitors (which antagonize the ability of the somatomedins to stimulate cartilage), we asked if changes in net somatomedin activity could involve progressive underlying alterations in levels of both somatomedins and somatomedin inhibitors. Groups of rats were killed during three days of fasting and 24 hours of refeeding. Fasting was associated with a rise in serum beta-hydroxybutyrate from 1.6 to 12.6 mmol/L after one day, followed by a decline to 4 mmol/L at three days. Somatomedins (low-MW) were separated from somatomedin inhibitors (high-MW) by gel permeation chromatography at acid pH on Sephadex G-50 and TSK-2000 HPLC. Somatomedins fell 35% after one day of fasting, and decreased to 59% below control levels after three days (P less than .05). Somatomedins did not change with six hours of refeeding, but then rose rapidly, reaching control levels after 24 hours. Somatomedins were correlated with change in weight (r = .41, P less than .05), but not with glucose or beta-hydroxybutyrate. Inhibitors rose to 195% above control-levels after one day of fasting, and continued to rise to 375% above control after three days (P less than .01). In contrast to the delayed change in somatomedins with refeeding, there was an abrupt fall in inhibitors (41% below three-day fasted levels after six hours), returning to control levels after 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1978

Comparison of [125I]somatomedin A and [125I]somatomedin C radioreceptor assays for somatomedin peptide content in whole and acid-chromatographed plasma.

The placental membrane radioreceptor assay was used to measure the levels of somatomedin (SM) peptides in plasma. Displacement of both [125I]somatomedin A ([125I]SM-A) and [125I]somatomedin C ([125I]SM-C) by normal whole plasma, the peptide fraction of acid-chromatographed plasma, and a partially purified, insulin-free SM preparation were compared. The peptide fraction of plasma was isolated by acid chromatography over Sephadex G-50 in 0.25 M formic acid with a yield of greater than or equal to 90%, as determined by bioassay and [125I]SM. In the case of [125I]SM-A, the dose-response curves for whole plasma, acid-chromatographed plasma, and the standard SM preparation were parallel (P less than 0.2). In contrast, for [125I]SM-C, the dose-response curves for acid-chromatographed plasma and the purified SM preparation were parallel (P less than 0.2), but both differed significantly from that of whole plasma (P less than 0.001). In addition, there was less variability in the assay of acid-chromatographed plasma compared to whole plasma. The results indicate that radioreceptor assay of unextracted normal plasma using [125I]SM-A is a valid measure of SM peptide concentration, while radioreceptor assay of unextracted normal plasma using [125I]SM-C, in our hands, is not. Acid chromatography of plasma before its assay is an uncomplicated procedure which allows valid and precise measurement of SM peptide content using either [125I]SM-A or [125I]SM-C.

Adult↗
PubMed1979

Further comparisons of the [125I]somatomedin A and the [125I]somatomedin C radioreceptor assays of somatomedin peptide.

The GH dependency of somatomedin (SM) peptide content in plasma was assessed using the placental membrane radioreceptor assay (RRA) to measure whole and acid-chromatographed plasma using both [125I]SM A and [125I]SM C. Plasmas from 10 normal children and adults, 11 GH-deficient children before and after therapy with 0.1 U/kg GH im daily for 5 days, and 10 acromegalic patients were assayed as well as a standard plasma pool from 20 healthy adult males. The results of these assays revealed that the SM content of plasma is GH dependent and that assay of whole and acid-chromatographed plasma with the [125I]SM A RRA and assay of acid-chromatographed plasma with the [125I]SM C RRA give comparable measurements of SM peptide content. There was a positive correlation of the [125I]SM A RRAs of whole and acid-chromatographed plasma from each patient (r = 0.87; n = 41; P much less than 0.001). An even stronger positive correlation was observed when the [125I]SM A and [125I]SM C RRAs of acid-chromatographed plasma were compared (r = 0.94; n = 41; P much less than 0.001). Furthermore, it was demonstrated that precise measurement of SM peptide content in plasmas from subjects with abnormal GH states and from normal subjects is enhanced by acid chromatography of the plasma before assay in either the [125I]SM A or [125I]SM C RRA.

Acromegaly↗
PubMed1985

Glucocorticoid effects on somatomedins and somatomedin inhibitors.

Glucocorticoid excess may be associated with poor growth despite normal levels of GH and adequate nutrition. Steroid-induced growth failure could be mediated by defective generation and/or action of somatomedins. To probe potential mechanisms, we examined the effect of corticosteroid administration on net somatomedin activity, immunoreactive somatomedin-C, and separated biologically active somatomedins and somatomedin inhibitors. Twelve children receiving alternate day steroid therapy had circulating somatomedin activity measured by porcine cartilage bioassay. Somatomedin activity fell 6 h after steroids [from 1.02 +/- 0.09 (+/- SEM) to 0.35 +/- 0.07 U/ml; P less than 0.001] and then rose toward normal. No significant change in somatomedin activity occurred during the day off therapy. Further studies were conducted in normal subjects given a single 60-mg dose of prednisone. Six hours after prednisone, somatomedin activity (rat cartilage bioassay) decreased by 46% (P less than 0.01), yet somatomedin-C did not change. To pursue this discrepancy, serum was fractionated on Sephadex G-50, pH 2.4, and separated somatomedin and somatomedin inhibitory bioactivity was measured. Biologically active somatomedins (Kav, 0.50-0.63) were comparable before and after prednisone treatment, as was inhibitory activity found at Kav 0.13-0.25. In contrast, somatomedin inhibitory activity at Kav 0.25-0.38 doubled (111 +/- 8% inhibition of somatomedin action vs. 54 +/- 11%; P less than 0.005) after prednisone therapy. The somatomedin inhibitor in these fractions blunted serum stimulation of sulfate, thymidine, and uridine uptake by test cartilage. These inhibitory effects could not be attributed to direct steroid action, as levels were less than 2 micrograms/dl in inhibitory fractions and addition of cortisol and prednisolone to the bioassay system failed to decrease somatomedin activity. We conclude that glucocorticoid administration is followed by an increase in circulating somatomedin inhibitors. Such inhibitors may explain the steroid-induced fall in net somatomedin activity and contribute to impaired growth.

Adolescent↗
PubMed1984

Nutrition and somatomedin. X. Comparison of insulin-like activity of somatomedins extracted from liver and serum.

Uncontrolled diabetes in rats is associated with reduced levels of both serum somatomedins and hepatic somatomedins. Hepatic somatomedins are recognized after extraction with 5 mol/L acetic acid, have a higher molecular weight (about 30,000) than serum somatomedins (about 8,000), despite acid conditions that dissociate somatomedins from circulating carrier proteins, and stimulate cartilage when given in vivo. To determine if hepatic somatomedins--as potential prohormones--have insulin-like activity comparable with serum somatomedins, their effects on rat epididymal adipose tissue were examined. Somatomedins were prepared from serum and liver extracts by gel filtration on Sephadex G-75, pH 2.4. In initial studies with fat pad segments, extracted hepatic somatomedins increased glucose oxidation only 64 +/- 11% above buffer (mean +/- SEM), while stimulation of 372 +/- 48% was provided by extracted serum somatomedins of comparable cartilage-stimulating potency (P less than 0.01, liver v serum). Further examination was performed with isolated adipocytes in a system sensitive to insulin at a concentration of 10 microU/mL (stimulation 100% above buffer). In dose-response studies measuring glucose oxidation, hepatic somatomedins had insulin-like activity of 16 microU/mL versus 55 microU/mL for serum somatomedins equipotent on cartilage (P less than 0.05); measuring glucose incorporation into total lipids, hepatic somatomedins had undetectable activity while serum somatomedins had activity of 28 microU/mL. It is concluded that hepatic somatomedins with potent cartilage-stimulating activity have greatly reduced insulin-like activity. The apparent dissociation in biologic activity of hepatic somatomedins suggests that while they may be prohormones, they may also represent a class of growth factors separate from the circulating somatomedins.

Adipose Tissue↗
PubMed1984

Stimulation of glycosaminoglycan synthesis by somatomedin and insulin in rat chondrocytes via somatomedin receptors.

Using cultured normal rat chondrocytes we have investigated 1) the effects of somatomedin and insulin on glycosaminoglycan (GAG) synthesis and 2) somatomedin and insulin binding sites. We confirmed that somatomedin and insulin stimulate GAG synthesis in normal rat chondrocytes. The maximal responses of somatomedin and insulin in GAG synthesis were the same, but the stimulation of GAG synthesis by maximally effective concentrations of insulin plus somatomedin was not cumulative. Cultured rat chondrocytes had binding sites for somatomedin and insulin, and the binding was displaced by both somatomedin and insulin. Somatomedin is much more effective than even large amounts of unlabelled insulin in displacing both somatomedin and insulin binding. Anti-insulin receptor IgG, which inhibits insulin binding to human placental membrane, did not affect GAG synthesis stimulated by insulin nor did it inhibit insulin binding to chondrocytes. Somatomedin used for GAG synthesis and displacement was the partially purified somatomedin A with a biological activity of 80 U/mg. Therefore the possibility that substances other than somatomedin A, which was contaminated in this preparation, affected this result could not be excluded completely. However, these results suggest that somatomedin and insulin act on normal rat chondrocytes through a somatomedin receptor.

Animals↗
PubMed1976

Nutrition and somatomedin. I. Effect of fasting and refeeding on serum somatomedin activity and cartilage growth activity in rats.

The relationship between nutrition, somatomedin, and growth was studied in young male rats which were fasted for 72 h, and then refed. Cartilage growth activity was measured by the incorporation of SO4 by costal cartilage incubated in vitro. Serum somatomedin activity was measured by the ability of sera to stimulate the incorporation of SO4 in vitro by cartilage from hypophysectomized rats or normal young pigs. Cartilage growth activity was unchanged after 24 h of fasting, but decreased significantly to hypopituitary levels after 72 h. The decrease in cartilage growth activity could not be attributed to a decrease in the ability of cartilage to respond to somatomedin, since fasted rat cartilage incubated in vitro had significantly greater stimulation from the addition of normal rat serum (normal somatomedin) than from the addition of hypophysectomized rat serum (low somatomedin). A decrease in serum somatomedin preceded the decrease in growth activity; somatomedin was significantly decreased after 24 h of fasting, and fell to hypopituitary levels after 72 h of fasting. The decrease in somatomedin could not be attributed to growth hormone deficiency, since treatment with bGH did not prevent the fall in somatomedin. The direct addition of fasted rat serum to normal rat serum did not inhibit the somatomedin activity of the normal serum. The refeeding of 72h-fasted rats was associated with an increase in serum somatomedin which was significant after 6 h, and comparable to control levels after 24 h of refeeding. The increase in somatomedin was followed by an increase in cartilage growth activity, which was significant after 12 h, and comparable to control levels after 48 h of refeeding. We conclude that adequate food intake appears to be required for the maintenance of normal levels of somatomedin; the processing of nutrients may modulate the generation of somatomedin.

Animal Nutritional Physiological Phenomena↗
PubMed1979

Further characterization of growth hormone-dependent somatomedin-binding proteins in rat serum and demonstration of somatomedin-binding proteins produced by rat liver cells in culture.

The somatomedin-like peptide multiplication-stimulating activity (MSA) binds specifically to rat serum. The pattern of MSA binding is GH dependent. Specific binding of [125I]iodo-MSA in normal rat serum is primarily in the gamma-globulin region (peak II) on Sephadex G-200, while MSA binding in hypophysectomized (hypox) rat serum is near the albumin region (peak III). This study further characterizes the peak II and peak III somatomedin-binding proteins produced by rat liver cells in culture. [125I]Iodo-MSA binding to normal rat serum is abolished by trypsin pretreatment of rat serum, suggesting that MSA binds to protein components of serum. The only detectable somatomedin activity (measured by [3H]thymidine incorporation into chick embryo fibroblast DNA) in fractions of normal rat serum chromatographed on Sephadex G-200 coincides with peak II binding of [125I]iodo-MSA. In hypox rat serum, the majority of detectable somatomedin activity is in the peak III region. There is complete displacement of the human somatomedins [125I]iodoinsulin-like growth factor I and II and [125I]iodosomatomedin A from the rat serum-binding sites by unlabeled MSA, suggesting that the human somatomedins bind to the same sites as MSA. Treatment of normal rat serum with 1 M acetic acid dissociates somatomedin activity from its binding proteins and converts somatomedin-binding proteins from peak II to peak III. Scatchard analysis of competitive binding data using [125I]iodo-MSA yields a binding affinity that is not appreciably different for either normal or hypox rat sera. The binding capacity of normal or acid-treated normal rat serum for MSA is significantly greater than that for comparably treated hypox rat sera. Although the site of synthesis of somatomedin-binding proteins in vivo is unknown, specific somatomedin-binding proteins are synthesized by two rat liver cell lines in culture. These rat liver cell somatomedin-binding proteins have the same molecular size and the same binding affinity for MSA as the peak III somatomedin-binding protein(s) in rat serum.

Animals↗
PubMed1987

Nutrition and somatomedin. XVII. Circulating somatomedin C during treatment of diabetic ketoacidosis.

Although somatomedin levels may be low in animals with experimental diabetes, values in humans have generally been normal. Because humans with severely decompensated diabetes have not been studied, we characterized somatomedin C responses during metabolic restoration in 21 patients with diabetic ketoacidosis. Somatomedin C values were compared with those of 25 outpatient controls. Somatomedin C in controls (mean +/- SE) was 0.72 +/- 0.09 U/ml, 69% of the mean sex-adjusted normal level; 28% of patients had values below the lower limit of normal. In ketoacidotic subjects, initial somatomedin C was 0.43 +/- .06 U/ml, 33% of the mean normal level; 52% of subjects had somatomedin C below the lower limit of normal. Initial levels in ketoacidotic subjects were unrelated to presenting levels of glucose, bicarbonate, ketones, or blood urea nitrogen but were significantly lower in patients of less than ideal body weight (0.30 vs. 0.58 U/ml, P less than .03). Presenting levels of somatomedin C in ketoacidotic subjects were significantly lower than in controls (P less than .02). During insulin-infusion therapy, somatomedin C rose to a peak of 1.16 +/- 0.21 U/ml after 28 h, significantly higher than initial levels (P less than .05). With continued subcutaneous insulin, somatomedin C fell to a nadir after an additional 22 h then rose more slowly to a final value of 0.75 +/- 0.12 U/ml, significantly higher than the nadir (P less than .05) but lower than peak values; final values in the ketoacidotic subjects were comparable to outpatient somatomedin C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Nutrition and somatomedin. XIII. Usefulness of somatomedin-C in nutritional assessment.

Malnutrition is common in hospitalized patients, but current measures of nutritional status are limited. Because levels of somatomedins are regulated by nutrition, the utility of somatomedin-C measurement in nutritional assessment was studied. Thirty-seven malnourished patients had measurement of somatomedin-C and conventional nutritional indexes. In 28 patients seen before therapy, the somatomedin-C level was reduced (38 percent of normal) and was lower than the albumin level (66 percent, p less than 0.01), transferrin level (59 percent, p less than 0.05), and lymphocyte count (43 percent, p = NS). Somatomedin-C level was lowest with combined "kwashiorkor-marasmus" (25 percent of normal) and also reduced with "kwashiorkor" (51 percent) or "marasmus" (57 percent) alone. Somatomedin-C was correlated with albumin, transferrin, and lymphocyte count (p less than 0.02 for each). In six patients given nutritional therapy, somatomedin-C levels rose by more than 70 percent in each (mean increase 181 percent), whereas lymphocyte counts rose in four (increase 78 percent for all patients), transferrin levels rose in four (increase 33 percent), and albumin levels rose in one (-6 percent). In 20 patients with detailed dietary analysis, only somatomedin-C was correlated with intake of protein and calories (p less than 0.005 for each). Somatomedin-C may be a sensitive marker of malnutrition and the response to nutritional therapy.

Adult↗
PubMed1990

Nutrition and somatomedin. XXI. Insulin-like growth factor-I and somatomedin inhibitor in streptozotocin-diabetic rats: relation to ketogenesis and gluconeogenesis.

Diabetes is associated with a fall in serum insulin-like growth factor-I (IGF-1) and a rise in somatomedin inhibitor, a circulating factor(s) of approximately 30,000 MW that is released by the liver and can antagonize both somatomedin and insulin action. Levels of inhibitor correlate with levels of glucose, beta-hydroxybutyrate, and weight loss. To study pathways that could underlie the fall in IGF-1 and rise in inhibitor, the effects of metabolic inhibitors on circulating metabolic fuels, serum IGF-1, and serum somatomedin inhibitor activity were studied. Rats given streptozotocin exhibited weight loss of 14% +/- 0.1%, glucose 457 +/- 26 mg/dL, and beta-hydroxybutyrate (BOHB) 6.3 +/- 0.5 mmol/L. Somatomedin inhibitor was separated from IGF-1 by size exclusion HPLC at pH 3; IGF-1 was measured by RIA, and somatomedin inhibitor by cartilage bioassay. Diabetic animals exhibited a fall in IGF-1 to 76% of normal (P less than .02) and a rise in inhibitor to 270% of normal (P less than .01). 3-Mercaptopicolinic (3-MPA) acid, an inhibitor of gluconeogenesis, lowered glucose to 68 +/- 2 mg/dL and BOHB to 0.96 +/- 0.09 mmol/L (both P less than .01 v diabetic), but levels of inhibitor did not fall. Nicotinic acid, an inhibitor of lipolysis, did not affect glucose but reduced BOHB to 0.42 +/- 0.02 mmol/L; somatomedin inhibitor fell 19% below diabetic levels (NS) but remained above normal (P less than .01). In contrast, inhibition of fatty acid oxidation with methyl-2-tetradecylglycidate reduced glucose to 191 +/- 18 mg/dL but lowered BOHB to normal, 0.16 +/- 0.02 mmol/L, accompanied by normalization of somatomedin inhibitor levels (152% +/- 33% of normal, NS). Below 1.0 mmol/L BOHB, somatomedin inhibitor and BOHB were strongly correlated (r = .67, P less than .001); no comparable relation was found with glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Nutrition and somatomedin. XI. Studies of somatomedin inhibitors in rats with streptozotocin-induced diabetes.

Diabetics may have normal somatomedins by radioimmunoassay yet decreased somatomedin activity by bioassay. The discrepancy appears due to circulating inhibitory factors; inhibitors in whole diabetic serum antagonize the action of both somatomedins and insulin via noncompetitive interactions. Since little is known about the nature of the inhibitory activity, serum from streptozotocin-diabetic rats was fractionated, and inhibitory activity measured as the ability of fractions to blunt stimulation of SO4 uptake by hypophysectomized rat costal cartilage exposed in vitro to somatomedins in normal rat serum. After establishing that inhibitory activity was stable to pH and lyophilization, diabetic rat serum was gel filtered at pH 7 (somatomedins bound to carrier proteins) and 2.4 (somatomedins dissociated, mol wt approximately 8000). Using Sephadex and Sephacryl columns at neutral pH, inhibitors were detected at mol wt approximately 250,000, approximately 24,000, and approximately 940. Predominant activity was at approximately 24,000 and approximately 940. In contrast, Sephadex columns at acid pH revealed inhibitors only at mol wt approximately 21,000. Diabetic rat serum was also subjected to ion-exchange chromatography on CM-Sepharose. A single band of activity at pH 5-7 was found on elution with increasing pH, suggesting an isoelectric point(s) lower than that of the somatomedins. However, three areas of activity were seen on elution with increasing ionic strength at pH 5-at 0.02 M and 0.14-1.4 M and at 2.0 M pH 5.0-5.5. These studies indicate that reduced anabolism in diabetes may be due in part to three species of circulating somatomedin inhibitors, largely of mol wt approximately 21-24,000 and approximately 940, and also of mol wt approximately 250,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Nutrition and somatomedin. XV. Growth plate, growth factor and biologically active somatomedins in rats with streptozotocin-induced diabetes.

Diabetic children may exhibit poor growth, yet levels of growth hormone and somatomedins measured by specific radioligand assays usually are normal. In the present studies, biological assays based on costal cartilage from hypophysectomized rats were used to test the possibility that diabetes is associated with decreases in circulating growth-related factors. 'Growth plate growth factor' activity was evaluated with tissue from the osteochondral junction (which resembles epiphyseal cartilage), and 'somatomedin' activity was measured with resting cartilage distant from the growth plate. Diabetes was induced in rats by administration of streptozotocin (STZ) at 40, 80, 160 and 310 mg/kg. Two days later, animals receiving STZ 40 mg/kg exhibited slight hyperglycemia but normal beta-hydroxybutyrate and weight gain; glucose and beta-hydroxybutyrate rose, and weight fell progressively with higher dosage. Gel filtration on Sephadex G-75 at pH 2.4 was used to separate rat serum into somatomedins (KAv 0.50-0.75) and growth plate growth factor (KAv 0.38-0.50). Somatomedins were 102, 92, 83 and 68% of control in STZ-treated animals, i.e. unchanged from control at 40 mg/kg STZ and falling only with higher dosage. In contrast, the growth plate growth factor declined at all doses of STZ to 93, 84, 69 and 57% of control. Thus, the growth plate growth factor began to fall with mild hyperglycemia alone (glucose 190 mg/dl), while a comparable fall in somatomedins was not seen until glucose was greater than 400 mg/dl and beta-hydroxybutyrate was three times normal. Only the growth plate growth factor was correlated with changes in body weight (r = 0.44, p less than 0.025). We conclude that decreases in levels of a circulating growth plate growth factor may contribute to growth impairment in diabetes. Measurements of this factor may be useful in examining underlying mechanisms.

Animals↗
PubMed1979

Nutrition and somatomedin. V. Action and measurement of somatomedin inhibitor(s) in serum from diabetic rats.

Serum from normal rats stimulates growth cartilage in vitro; this stimulation is attributed to somatomedin activity. In contrast, serum from diabetic rats may produce dose-response lines with negative slopes and, in combination studies, suppress the stimulatory activity of serum from normal rats; this is attributed to somatomedin inhibitory factor(s). Somatomedin inhibitory activity in serum from diabetic rats cannot be attributed to recognized catabolic factors, such as glucocorticoids or free fatty acids. The inhibitory activity is resistant to 100 C heat at neutral pH but is partially removed by 100 C heat at pH 5.5. Somatomedin inhibitory activity can be estimated as the ability to decrease the stimulation of rat cartilage incubated for 2 days with serum from normal rats. With this method, serum from diabetic rats provides linear inhibition of both sulfate and thymidine uptake. This procedure is simple, reproducible, and allows detection of inhibitory activity in as little as 5 microliter whole serum. It allows identification of individual samples enriched in inhibitory activity and should be useful in further studies of somatomedin inhibitory factor(s).

Animals↗