|ISSN No. 1606-7754 Vol.12 No.3 December 2004|
Exocrine pancreatic insufficiency in diabetes mellitus
Jaipaul Singh1 Ernest Adeghate2, Sarah Aparico1, Richard Hopkin1
1Department of Biological Sciences, University of Central Lancashire, U.K., & 2Department of Human Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al-Ain, United Arab Emirates.
Diabetes mellitus (DM) is a major global health problem and it currently affects more than 175 million people worldwide. DM is an increasingly common chronic disorder which is associated with substantial costs in terms of life and demand on health budgets. Thus, up to 15% of national budgets are spent on the diagnosis, treatment and caring of diabetic patients in the Western World. DM is divided into two main groups, Type 1 or Insulin –dependent diabetes mellitus (IDDM; 5-10 % of all cases and juvenile onset) and Type 2 or Non-insulin- dependent diabetes mellitus (NIDDM; 90-95 % of all cases and adult in onset). Both Types 1 and 2 DM are associated with a number of common symptoms and long term complications. One of these is the indigestion of food stuffs, especially carbohydrates. This is due to the inability of the gastrointestinal tract, especially the salivary glands and the exocrine pancreas to secrete an adequate amount of the major digestive enzyme, amylase. The medical term used to describe the dysfunction is digestive insufficiency or exocrine pancreatic insufficiency when dealing with the pancreas alone. Current evidence in the literature suggests that exocrine pancreatic insufficiency may be associated with a number of physiological and biochemical processes which may be deranged in the pancreas. These include reduced endogenous insulin secretion or insensitivity of the islet hormone to regulate glucose metabolism especially by pancreatic acinar cells, reduced gene expression for the mRNA amylase and the synthesis and release of the enzyme, reduced cytosolic concentrations of calcium (Ca2+) and magnesium (Mg2+), reduced Na+-K+-ATPase and tyrosine kinase activities and insensitivity of cholecystokinin (CCK) receptors on pancreatic acinar cells. This review describes the cellular mechanism of exocrine pancreatic insufficiency in DM compared to healthy conditions. The work focuses on a brief review of DM, the normal anatomy and physiology of the pancreas, stimulus-secretion coupling and the interactions between secretagogues, DM–induced exocrine pancreatic insufficiency and the roles of a number of cellular mediators in the stimulus- secretion coupling processes, the cellular and molecular mechanisms associated with the disease and finally, on the scope for future research studies.
Keywords : Exocrine pancreas, insulin, amylase mRNA, calcium, diabetes mellitus, pancreatic insufficiency
Diabetes mellitus (DM) is a major global health problem affecting at least 175 million people worldwide. The disease is an increasingly prevalent chronic disorder and is a life-threatening condition. The World Health Organization estimates that, worldwide, the burden of premature death from DM is now as great as that imposed by HIV/AIDS.1 This premature loss of life amongst sufferers is greatest in developing nations, and most of the predicted increase in the incidence of diabetes in the next 25 years (approximately doubling the number of sufferers by 2030) will occur in the developing world.1
DM is divided into two types, type 1 or insulin dependent diabetes mellitus (IDDM; 5-10 % of all cases and juvenile in onset) and type 2 or non-insulin- dependent diabetes mellitus (NIDDM; 90-95 % of all cases and adult in onset). Both types 1 and 2 DM have a number of common symptoms and long-term complications. One is the poor digestion of foodstuffs, especially carbohydrates. This is a consequence of the inability of the gastrointestinal tract, especially the salivary glands and the exocrine pancreas to secrete an adequate amount of a major digestive carbohydrase, amylase. Exocrine pancreatic insufficiency is the consequence of a derangement in physiological and biochemical processes in the pancreas. These include reduced endogenous insulin secretion, failure of insulin to regulate glucose metabolism, reduced expression of amylase mRNA, reduced cytosolic concentrations of calcium (Ca2+) and magnesium (Mg2+), reduced Na+-K+-ATPase and tyrosine kinase activities and an insensitivity of cholecystokinin (CCK) receptors on pancreatic acinar cells. This review focuses on the cellular mechanisms of exocrine pancreatic insufficiency. We consider the ontogeny, anatomy and physiology of the pancreas and stimulus-secretion coupling, as well as DM–induced exocrine pancreatic insufficiency. We also discuss the roles of receptors and cellular mediators in the stimulus-secretion coupling processes.