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growth hormone control control days after pancreatectomy

FIGURE 15 Requirement of insulin for normal growth in response to GH. All rats were pancreatectomized 3 to 7 weeks before the experiment was begun. Each rat was fed 7 g of food per day. The treated group was injected with the indicated amounts of growth hormone daily. Note the failure to respond to GH in the period between 20 and 44 days, coincident with the decrease in daily insulin dose, and the resumption of growth when the daily dose of insulin was restored. (From Scow RO, Wagner EM, and Ronov E, Endocrinology 1958; 62:593-604. With permission.)

Optimal concentrations of insulin in blood are required to maintain normal growth during postnatal life, but it has been difficult to obtain a precise definition of the role of insulin. Because life cannot be maintained for long without insulin, dramatic effects of sustained deficiency on final adult size are not seen; however, growth is often retarded in insulin-dependent diabetic children, particularly in the months leading up to the diagnosis of full-blown disease. Studies in pancreatecto-mized rats indicate a direct relation between the effectiveness of GH and the dose of insulin administered. Treatment with GH sustained a rapid rate of growth as long as the daily dose of insulin was adequate, but growth progressively decreased as the dose of insulin was reduced (Fig. 15). Conversely, insulin cannot sustain a normal rate of growth in the absence of GH.

The effects of insulin on postnatal growth cannot be attributed to changes in GH secretion, which, if anything, is increased in human diabetics. Although insulin was sometimes used diagnostically to provoke GH secretion, it is the resulting hypoglycemia, rather than insulin per se, that stimulates GH release. Expression of IGF-I mRNA in liver and other tissues is decreased in diabetes and in low insulin states such as fasting or caloric restriction, consistent with the possibility that insulin is permissive for growth. Insulin stimulates protein synthesis and inhibits protein degradation; in its absence, protein breakdown is severe. Consequently, without insulin, normal responses to GH are not seen; the anabolic effects of GH on body protein either cannot be expressed or are masked by simultaneous, unchecked catabolic processes.

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