The life story of the pancreatic B cell

Abstract

Summary. Most research on the pancreatic B cell has so far focussed on the regulation and molecular biology of insulin biosynthesis and release. The present review draws attention to some additional areas of islet research which have become accessible to investigation by recent methodological progress and which may advance our understanding of the role of the B cell in diabetes. There is now evidence to suggest that B cells arise from a pool of undifferentiated precursor cells in the fetal and newborn pancreas. These ceils may contribute to islet growth and, if inappropriately stimulated, also to early islet hyperplasia. In the postnatal state, B-cell function is finely tuned by a complex set of incoming signals, one of which is the nutrient supply provided by the blood. Recent studies indicate that a disproportionately high fraction of pancreatic blood is diverted to the islets and that the islet blood flow is increased by glucose. An acute stimulus to insulin release may thus be accompanied by a process which enhances the distribution of the hormone to the target cells. Long-term adjustments of B-cell function are made by changes in B-cell number and total mass. Adaptive growth responses to an increased insulin demand occur in a number of hereditary diabetic syndromes in animals, but in some of these there is an inherited restriction on the capacity for B-cell proliferation leading to further deterioration of the glucose tolerance. Some evidence suggests that a similar mechanism may operate also in human non-insulin-dependent diabetes. A critical appraisal of this hypothesis requires, however, that human B cells should be tested for their growth characteristics. Studies of B-cell proliferation in experimental animals have shown that the B cell passes through the cell cycle at a relatively high rate but that the fraction of proliferating cells is low. Regulation of growth of the total B-cell mass seems to take place by changes in the number of B cells passing through the cell cycle rather than by changes in the rate of the cycle. The number of proliferating B cells also shows a marked decrease with age. It is at present uncertain to what extent these regulatory mechanisms apply also to the human B cell but it can be anticipated that further technical developments will elucidate this problem.

Effect of partial pancreatectomy on diabetic status in BALB/c mice

“…Our pancreatectomy procedure was based on the requirement to keep the ductal pancreas intact, to induce the stem cells to switch into a regenerative or proliferative phase, and our experimental data indeed demonstrated induction of the expected regenerative process. Our findings do not agree with those of Okamoto (1985) and Yonemura et al (1984), whose pancreatectomised animals (like the CPx group in our study) exhibited glucosuria during their 3-month follow-up study after 90% pancreatectomy, but rather our data support the work of Bonner-Weir et al (1993) and the hypothesis of a ductal origin of islet stem cells (Hellerstrom 1984, Rosenberg & Vinik 1992, Bonner-Weir et al 1993. This stem cell population in the pancreatic duct has been extensively studied, but the factor(s) responsible for directing stem cells towards pancreatic regeneration remain largely unknown.…”

“…Increase in pancreatic -cell mass may result from mitotic proliferation of pre-existing islet cells, or islets may bud off from the ductal system of the pancreas (Slack 1995), arise from transformation of the acini into new islets, or may even be derived from the centro-acinar cells ( Jindal et al 1995). There is strong evidence that islet stem cells may exist in the pancreatic duct (Hellerstrom 1984, Bonner-Weir et al 1993 and that these ductal epithelial cells may be switched into a proliferative/regenerative phase leading to nesidioblastosis. In mammals, organs such as the liver and pancreas are well known to inherit a strong regenerative potential; however, the process of regeneration has to be preceded by an operative insult that involves removal of a part of the entire organ (Michalopoulos & DeFrances 1997).…”

Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes

“…Therefore, our new in vitro model of the pathological development of GK pancreatic rudiment represents a major tool for understanding the events implied in GK beta cell anomaly. As previously indicated, beta cells appear during organogenesis from the replication of pre-existing beta cells and mainly from the recruitment and maturation of undifferentiated beta cell precursors [36]. The present study suggests that GK beta cell deficiency resulted from decreased beta cell proliferation, a defect in beta cell neogenesis from precursors and increased apoptosis in beta cells and their precursors.…”

Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

“…Even when, during foetal and neonatal life, islets are newly formed from precursor cells that bud off from the pancreatic ducts (Swenne 1982, Hellerström 1984, only a low degree of neogenesis exists in the adult, this mechanism being enhanced under strong stimuli (Bonner-Weir 2000). CKs are considered good markers of the neogenetic area from which cells, originating in the ductal epithelium (protodifferentiated stem cells), are added to the islet mass (Bouwens et al 1994, Wang et al 1995.…”