Morphine, Opioid Peptides, and Pancreatic Islet Function

Abstract

Since the isolation of enkephalins 7 yr ago, there has been an explosive increase in knowledge and an enormous interest in the action of both exogenous and endogenous opiates. This review deals with the interaction of opiates with the endocrine pancreas. The results of animal studies performed in vitro do not allow any conclusion to be drawn, because the effects of opioid peptides on pancreatic hormone release seem dependent on many variables, including the agent investigated, dose administered, concentration of glucose in the medium, and experimental procedure used. The results of in vivo animal studies suggest that central administration of opiates and opioid peptides acts indirectly via the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion, while peripheral administration tends to stimulate insulin and glucagon secretion. This last statement seems also to be true for studies performed in human beings. The narcotic addict offers a model to evaluate the hormonal and metabolic effects of a chronically administered agent that binds and activates endogenous receptors. In these subjects, it is possible to find increased concentrations of glycosylated hemoglobin A1 and a marked reduction of the acute insulin response to intravenous glucose, but not to arginine, which suggests a state of defective glucose recognition by pancreatic β-cells during narcotic addiction. Thus, the heroin addict, like patients with non-insulin-dependent diabetes, does not respond appropriately to glucose signals. Moreover, naloxone, an opiate-receptor blocking agent, can cause a partial restoration of the acute insulin response to i.v. glucose in some subjects with non-insulin-dependent diabetes. An increased sensitivity to endogenous opiates—enkephalins—might be important in the pathogenesis of non-insulin-dependent diabetes in human beings.