Nutrition and somatomedin. IX. Blunting of insulin-like activity by inhibitor in diabetic rat serum.
Poor growth in uncontrolled experimental diabetes appears due in part to increased circulating inhibitor, a factor (or factors) that blocks stimulation of growing cartilage by somatomedins. To determine if the inhibitor has other antianabolic properties, we examined effects on insulin and insulin-like action on muscle and adipose tissue. Rat epididymal fat pads were exposed to normal rat serum, somatomedins (fraction from normal rat serum) or insulin, with or without added streptozotocin-diabetic rat serum or inhibitor (fraction from diabetic serum); insulin-like activity was assessed by glucose conversion to CO2. Diabetic rat serum alone lowered glucose utilization significantly below buffer levels (P less than .010), but inhibitor alone had no effect. However, stimulation by insulin, normal rat serum, or somatomedins was decreased significantly by both diabetic rat serum or inhibitor (P less than 0.01); Lineweaver-Burk analysis suggested that such inhibition was noncompetitive. In incubations with rat diaphragm, neither diabetic rat serum nor inhibitor alone lowered glucose incorporation into glycogen, but both inhibited muscle stimulation by insulin (P less than 0.01). In in vivo studies, rats given insulin with added diabetic rat serum exhibited decreased stimulation of glucose incorporation into muscle glycogen (P less than 0.01) and into adipose tissue total lipids. These observations indicate that an inhibitor in the serum of diabetic rats can brake anabolic processes is muscle (glycogen formation) and adipose tissue (glucose utilization, lipid formation). Such an inhibitor may therefore contribute to poor growth in diabetes by decreasing calorie storage due to insulin and insulin-like actions as well as skeletal elongation due to somatomedin action.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005947:Glucose / Q000378:metabolism; D006131:Growth Inhibitors / Q000097:blood / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin; D007329:Insulin Antagonists; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013002:Somatomedins / Q000037:antagonists & inhibitors / Q000097:blood
D006131:Growth Inhibitors; D007328:Insulin; D007329:Insulin Antagonists; D013002:Somatomedins; C021250:somatomedin inhibitor; D005947:Glucose