Table 1.

Normal physiological role of insulin/IGF family members.

	Origin	Gene regulation	Serum levels	Affinity for insulin/IGF family members	Function
Insulin	Beta cells of the pancreas	Glucose uptake, protein synthesis	11–14 μU/mL	IR >IGF-IR> IGF-IIR	–Regulates carbohydrate, fat, and protein metabolism.
					–Mitogenic effect.
IGF-I	Liver, bone, and several other tissues.	Hormones, growth factors, cytokines, nutrition, smoking, exercise.	100–200 ng/mL	IGF-IR> IGF-IIR > IR	–Regulates embryonic growth and specific differentiation in adult tissues.
					–Involved in cell proliferation, transformation, and antiapoptotic activity.
IGF-II	Liver, kidney, bone, and several other tissues.	Tumor suppressor proteins WT1 and p53, HIF-1, genomic imprinting.	400–700 ng/mL	IGF-IIR> IGF-IR>IR	–Functional during embryonic and fetal growth.
IGFBPs	IGFBP-1: liver, decidua.	BP-1: insulin, steroids.	BP-1, BP-2: vary during the day and meals.	BP-1, BP-3, BP-5: IGF-I> IGF-II	–Regulate transport and half-life of IGFs between different body compartments.
	IGFBP-2: CNS.	BP-2: insulin, metabolic process.
	IGFBP-3: several tissues.	BP-3: GH, PTH, cytokines, p53, estradiol, steroids.
	IGFBP-4: bone, CNS, prostate.	BP-4: vitamin D, parathyroid hormone.	BP-3: vary in relation to age and sex 1500–5580 ng/mL.	BP-2, BP-6: IGF-II>IGF-I	–Regulate IGF independent effect on cell proliferation and apoptosis.
	IGFBP-5: kidney, bone, mammary gland.	BP-5: GH, prolactin, vitamin D.
	IGFBP-6: ovary, prostate.	BP-6: GH, FSH.