Induction of endocrine cell differentiation: a new approach to management of diabetes.
Cellophane wrapping of the hamster pancreas induces a trophic stimulus that leads to ductular proliferation in association with nesidioblastosis. Our previous studies have demonstrated that cellophane wrapping of the pancreas leads to the development of a new population of beta-cells that is capable of reversing streptozocin-induced diabetes. The predominant type of islet regenerated is initially small but progressively enlarges to the size of control islets. Electron microscopy and immunocytochemistry revealed areas of nesidioblastosis that contained a predominance of beta-cells, but also alpha- and delta-cells. Metabolic studies were conducted to define the functional aspects of this model. After cellophane wrapping of the normal hamster pancreas, normal serum levels of glucose and insulin were maintained despite a 2.5-fold increase in the number of pancreatic islets per square millimeter compared with a control group that underwent a sham operation and was not wrapped. Islets were harvested from control and cellophane-wrapped pancreata and demonstrated a similar biphasic insulin response to high-dose glucose perfusion in vitro. Insulin secretion ceased with low-dose glucose perfusion. Insulin derived from unwrapped pancreata was found to comprise two peaks on high-pressure liquid chromatography and that from wrapped pancreata a single peak. The biologically active insulin corresponded on high-pressure liquid chromatography with the standard insulin preparation. Thus, the experimental induction of nesidioblastosis is associated with development of normal beta-cell sensitivity to glucose and release of a single form of a biologically active insulin. It thus represents a possible therapeutic approach to diabetes.
Rosenberg
L
L
Department of Surgery, Montreal General Hospital, Quebec, Canada.
Vinik
A I
AI
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002455:Cell Division; D002476:Cellophane; D006224:Cricetinae; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008647:Mesocricetus; D010179:Pancreas / Q000166:cytology / Q000601:surgery*; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D002476:Cellophane; D005947:Glucose