Insulin-like growth factors I and II (IGF-I and IGF-II) are expressed at high levels in the endocrine pancreas during development and tissue regeneration. However, their effects at the endocrine pancreas are poorly understood. We searched for receptors of IGF-I and IGF-II and possible biological effects on clonal insulin-secreting (HIT), glucagon-secreting (INR1G9), and somatostatin-secreting (RIN 1027 B2) cell lines. Our data showed that HIT cells and RIN 1027 B2 cells express specific type I and type 11 IGF receptors. INR1G9 cells possess type II IGF receptors and IGF-I binding sites with the same affinity for both IGF-I and IGF-II. In HIT cells, insulin secretion was not influenced by either peptide. Proinsulin gene transcription was stimulated by IGF-II but not by IGF-I. IGF-I potently inhibited proglucagon gene transcription and glucagon secretion in INR1G9 cells, whereas IGF-II only inhibited glucagon release. In RIN 1027 B2 cells, IGF-I but not IGF-II increased somatostatin output, whereas both stimulated somatostatin gene expression. These data demonstrate the presence of classic type I and type II IGF receptors on insulin-, glucagon-, and somatostatin-secreting cells. Both peptides may be important regulators of endocrine pancreatic function in terms of islet hormone release and gene expression. Therefore, both peptides may be involved in the regulation of intraislet cellular homeostasis.