50
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Aims/hypothesis

          We sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy.

          Methods

          Pancreas was obtained at autopsy from women who had died while pregnant ( n = 18), post-partum ( n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cell neogenesis (insulin-positive cells in ducts and scattered beta cells in pancreas).

          Results

          The pancreatic fractional beta cell area was increased by ∼1.4-fold in human pregnancy, with no change in mean beta cell size. In pregnancy there were more small islets rather than an increase in islet size or beta cells per islet. No increase in beta cell replication or change in beta cell apoptosis was detected, but duct cells positive for insulin and scattered beta cells were increased with pregnancy.

          Conclusions/interpretation

          The adaptive increase in beta cell numbers in human pregnancy is not as great as in most reports in rodents. This increase in humans is achieved by increased numbers of beta cells in apparently new small islets, rather than duplication of beta cells in existing islets, which is characteristic of pregnancy in rodents.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00125-010-1809-6) contains supplementary material, which is available to authorised users.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Pancreatic beta-cell mass in European subjects with type 2 diabetes.

          Decreases in both beta-cell function and number can contribute to insulin deficiency in type 2 diabetes. Here, we quantified the beta-cell mass in pancreas obtained at autopsy of 57 type 2 diabetic (T2D) and 52 non-diabetic subjects of European origin. Sections from the body and tail were immunostained for insulin. The beta-cell mass was calculated from the volume density of beta-cells (measured by point-counting methods) and the weight of the pancreas. The pancreatic insulin concentration was measured in some of the subjects. beta-cell mass increased only slightly with body mass index (BMI). After matching for BMI, the beta-cell mass was 41% (BMI 15 years of overt diabetes respectively). Pancreatic insulin concentration was 30% lower in patients. In conclusion, the average beta-cell mass is about 39% lower in T2D subjects compared with matched controls. Its decrease with duration of the disease could be a consequence of diabetes that, with further impairment of insulin secretion, contributes to the progressive deterioration of glucose homeostasis. We do not believe that the small difference in beta-cell mass observed within 5 years of onset could cause diabetes in the absence of beta-cell dysfunction.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes.

            Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas.

              Novel strategies in diabetes therapy would obviously benefit from the use of beta (beta) cell stem/progenitor cells. However, whether or not adult beta cell progenitors exist is one of the most controversial issues in today's diabetes research. Guided by the expression of Neurogenin 3 (Ngn3), the earliest islet cell-specific transcription factor in embryonic development, we show that beta cell progenitors can be activated in injured adult mouse pancreas and are located in the ductal lining. Differentiation of the adult progenitors is Ngn3 dependent and gives rise to all islet cell types, including glucose responsive beta cells that subsequently proliferate, both in situ and when cultured in embryonic pancreas explants. Multipotent progenitor cells thus exist in the pancreas of adult mice and can be activated cell autonomously to increase the functional beta cell mass by differentiation and proliferation rather than by self-duplication of pre-existing beta cells only.
                Bookmark

                Author and article information

                Contributors
                pbutler@mednet.ucla.edu
                Journal
                Diabetologia
                Diabetologia
                Springer-Verlag (Berlin/Heidelberg )
                0012-186X
                1432-0428
                5 June 2010
                5 June 2010
                October 2010
                : 53
                : 10
                : 2167-2176
                Affiliations
                [1 ]Larry L. Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 900 Veteran Ave, 24-130 Warren Hall, Los Angeles, CA 90095-7073 USA
                [2 ]Endocrine Research Unit, Department of Medicine, Mayo Clinic and Medical School, Rochester, MN USA
                [3 ]Department of Information Engineering, University of Padua, Padua, Italy
                Article
                1809
                10.1007/s00125-010-1809-6
                2931643
                20523966
                f5b0bacb-8452-4566-afe4-c1608922cdff
                © The Author(s) 2010
                History
                : 5 February 2010
                : 6 May 2010
                Categories
                Article
                Custom metadata
                © Springer-Verlag 2010

                Endocrinology & Diabetes
                human,pregnancy,islet,pancreas
                Endocrinology & Diabetes
                human, pregnancy, islet, pancreas

                Comments

                Comment on this article