Somatostatin receptors in congenital hyperinsulinism: Biology to bedside

Abstract

Congenital hyperinsulinism (CHI), although a rare disease, is an important cause of severe hypoglycemia in early infancy and childhood, causing preventable morbidity and mortality. Prompt diagnosis and appropriate treatment is necessary to prevent hypoglycaemia mediated brain damage. At present, the medical treatment of CHI is limited to diazoxide as first line and synthetic somatostatin receptor ligands (SRLs) as second line options; therefore understanding somatostatin biology and treatment perspectives is important. Under healthy conditions, somatostatin secreted from pancreatic islet δ-cells reduces insulin release through somatostatin receptor induced cAMP-mediated downregulation and paracrine inhibition of β- cells. Several SRLs with extended duration of action are now commercially available and are being used off-label in CHI patients. Efficacy remains variable with the present generation of SRLs, with treatment effect often being compromised by loss of initial response and adverse effects such as bowel ischaemia and hepatobiliary dysfunction. In this review we have addressed the biology of the somatostatin system contexualised to CHI. We have discussed the clinical use, limitations, and complications of somatostatin agonists and new and emerging therapies for CHI.

Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins

“…In our case, the lack of efficiency despite the growing doses prompted us to discontinue the treatment and start administering a different SSA, Pasireotide, which exhibits moderate affinity towards SSTR2 and SSTR3 ( 19 ). It also demonstrates superior affinity towards SSTR5 compared to Octreotide.…”

Oral SSTR5 Antagonist SCO‐240 for Growth Hormone Stimulation: A Phase I Single‐Dose Study in Healthy Individuals

“…1 Somatostatin exists in 2 forms, somatostatin-14 and somatostatin-28, which bind to a family of five somatostatin receptor subtypes (SSTR1-5) that are class A Gαiprotein-coupled receptors functionally coupled to the inhibition of adenylate cyclase, resulting in decreased cellular cAMP levels. 2…”

“…Somatostatin is a peptide hormone produced in brain cells, pancreatic islets, and the gut 1 . Somatostatin exists in 2 forms, somatostatin‐14 and somatostatin‐28, which bind to a family of five somatostatin receptor subtypes (SSTR1–5) that are class A Gαi‐protein‐coupled receptors functionally coupled to the inhibition of adenylate cyclase, resulting in decreased cellular cAMP levels 2 . In humans, SSTRs are expressed in the brain, anterior pituitary, pancreatic islets, adrenal cortex, medulla, thyroid, ovaries, testes, kidneys, lungs, myocardium, and skeletal muscle 3 .…”