Insulin-like growth factor-I and diabetes. A review.
Although diabetes is a heterogeneous condition, IGF-I has been shown to improve glycaemic control and reduce insulin requirements in both IDDM and NIDDM. In IDDM, the therapeutic rationale for IGF-I is as a replacement therapy "topping up" low circulating IGF-I levels. There is now convincing evidence that this is associated with a reduction in GH secretion resulting in an improvement in insulin sensitivity and glycaemic control. The mechanism may simply be reduced GH-secretion, but pre- and post-receptor effects on insulin sensitivity are also likely. It is not clear what effect IGF-I treatment has on IGF binding proteins, but with the restoration of a more normal GH/IGF-I axis they are likely to be restored to normal concentrations which may in turn have a direct effect on glucose metabolism. In NIDDM, the mechanism of action of IGF-I remains unclear. At high doses, IGF-I may mimic insulin, but at levels resulting in unacceptable "acromegalic" IGF-I levels and side-effects. The most exciting data concerning IGF-I is with a low dose where IGF-I improves insulin sensitivity by an unknown mechanism. This may be mediated via the IGF-I receptor, by cross-reactivity with the insulin receptor, or by activation of hybrid receptors. The exact mechanism and interaction remains to be elucidated. In severe insulin-resistant states, IGF-I-treatment appears to be effective, and may be the only realistic therapeutic measure in the near future, and warrants further investigation. Detailed genetic characterization of these syndromes following treatment with IGF-I may also help to characterize the mechanism of action of IGF-I and its interactions with the insulin receptor. Thus, IGF-I appears to have a future as a therapeutic agent in treating diabetes, but long-term studies addressing safety and short-term studies addressing mechanisms are essential. With only a few pharmaceutical companies having the capability to produce IGF-I for scientific and therapeutic investigation, it is important that short-term marketing strategy does not prevent the proper exploration of this exciting peptide hormone as a therapeutic agent for all types of diabetes.
Simpson
H L
HL
Division of Medicine, UMDS, St Thomas' Hospital, London, UK.
Umpleby
A M
AM
Russell-Jones
D L
DL
D003920:Diabetes Mellitus / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D008074:Lipoproteins; D007334:Insulin-Like Growth Factor I; D005947:Glucose