Pancreatic Alpha Cell Mass Across Adult Human Lifespan.

AIM To establish pancreatic alpha-cell mass in lean non-diabetic humans over the adult lifespan, performed as a follow up study to beta cell mass across the adult human lifespan. METHODS We examined human pancreatic autopsy tissue from 66 lean non-diabetic individuals aged from 30-102 years, grouped into deciles: 3rd(30-39 years), 4th(40-49 years), 5th(50-59 years), 6th(60-69 years), 7th(70-79 years), 8th(80-89 years) and 9th deciles(90+ years). Sections of pancreas were immunostained for glucagon and analyzed for fractional alpha-cell area. Population-based pancreatic volume data was used to calculate alpha-cell mass. RESULTS With advanced age, the exocrine pancreas undergoes atrophy demonstrated by increased fat area (as % exocrine area) (0.05±0.01 vs 1.6±0.7% fat area of total exocrine pancreas, 3rd vs 9th decile, p<0.05). Consequently, islet density increases with age (2.7±0.4 vs 10.5±3.3 islets/mm2, 3rd vs 9th decile, p<0.05). Alpha-cell fractional area increases with advanced age (0.34±0.05% vs 0.73±0.26%, 3rd vs 9th decile, p<0.05). However, alpha-cell mass remains constant at ~190mg throughout the adult lifespan in lean non-diabetic humans. Within islets, alpha-cell distribution between mantle and core is unchanged across deciles (1862±220 vs 1945±200 vs 1948±139 alpha-cells in islet mantle/mm2, 3rd vs 6th vs 9th decile, p=0.93 and 1912±442 vs 1449±123 vs 1514±168 alpha-cells in islet core/mm2, 3rd vs 6th vs 9th decile, p=0.47), suggesting that human islets retain their structural organization in the setting of age-related exocrine atrophy. CONCLUSIONS Consistent with our previous findings for beta-cell mass, alpha-cell mass remains constant in humans, even with advanced age. Pancreatic endocrine cells are much more robustly preserved than exocrine cells in aged humans and islets maintain their structural integrity throughout life.

[1]  Renu Gupta,et al.  Morphology and Aging of the Human Adult Pancreas: An Electron Microscopic Study , 2018 .

[2]  R. Mallone,et al.  Decreased α-cell mass and early structural alterations of the exocrine pancreas in patients with type 1 diabetes: An analysis based on the nPOD repository , 2018, PloS one.

[3]  T. Rabelink,et al.  Pancreatic α‐cell mass in obesity , 2017, Diabetes, obesity & metabolism.

[4]  P. Butler,et al.  Evaluation of immunohistochemical staining for glucagon in human pancreatic tissue , 2016, Journal of histotechnology.

[5]  H. Itoh,et al.  Effects of Glucocorticoid Treatment on β- and α-Cell Mass in Japanese Adults With and Without Diabetes , 2015, Diabetes.

[6]  H. Itoh,et al.  Change in β-cell mass in Japanese nondiabetic obese individuals. , 2013, The Journal of clinical endocrinology and metabolism.

[7]  R. Rizza,et al.  β-Cell Mass and Turnover in Humans , 2012, Diabetes Care.

[8]  R. Rizza,et al.  b-Cell Mass and Turnover in Humans Effects of obesity and aging , 2012 .

[9]  J. Henquin,et al.  Pancreatic alpha cell mass in European subjects with type 2 diabetes , 2011, Diabetologia.

[10]  C. Cobelli,et al.  Ongoing β-Cell Turnover in Adult Nonhuman Primates Is Not Adaptively Increased in Streptozotocin-Induced Diabetes , 2011, Diabetes.

[11]  T. Berney,et al.  Unique Arrangement of α- and β-Cells in Human Islets of Langerhans , 2010, Diabetes.

[12]  A. Çoker,et al.  Fat replacement of the malignant pancreatic tissue after neoadjuvant therapy , 2010, International Journal of Clinical Oncology.

[13]  C. Sempoux,et al.  Pancreatic β‐cell mass in European subjects with type 2 diabetes , 2008, Diabetes, obesity & metabolism.

[14]  Victor Couture,et al.  Appendix for online publication , 2007 .

[15]  B. Soria,et al.  Different Metabolic Responses in α-, β-, and δ-Cells of the Islet of Langerhans Monitored by Redox Confocal Microscopy , 2006 .

[16]  Camillo Ricordi,et al.  The unique cytoarchitecture of human pancreatic islets has implications for islet cell function , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[17]  B. Soria,et al.  Different metabolic responses in alpha-, beta-, and delta-cells of the islet of Langerhans monitored by redox confocal microscopy. , 2006, Biophysical journal.

[18]  J. Foley,et al.  Alpha cell function in health and disease: influence of glucagon-like peptide-1 , 2005, Diabetologia.

[19]  K. Chiu,et al.  Comparison of the relationship of age and beta cell function in three ethnic groups , 2005, Clinical endocrinology.

[20]  S. Kahn,et al.  Impact of Intra-Abdominal Fat and Age on Insulin Sensitivity and β-Cell Function , 2004 .

[21]  S. Kahn,et al.  Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function. , 2004, Diabetes.

[22]  Jae-Hyoung Cho,et al.  Selective β-Cell Loss and α-Cell Expansion in Patients with Type 2 Diabetes Mellitus in Korea , 2003 .

[23]  In Kyu Lee,et al.  Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. , 2003, The Journal of clinical endocrinology and metabolism.

[24]  B. Ahrén,et al.  Islet dysfunction in insulin resistance involves impaired insulin secretion and increased glucagon secretion in postmenopausal women with impaired glucose tolerance. , 2000, Diabetes care.

[25]  Angel Nadal,et al.  Homologous and heterologous asynchronicity between identified α‐, β‐ and δ‐cells within intact islets of Langerhans in the mouse , 1999 .

[26]  B. Soria,et al.  Homologous and heterologous asynchronicity between identified alpha-, beta- and delta-cells within intact islets of Langerhans in the mouse. , 1999, The Journal of physiology.

[27]  J. Friberg,et al.  Total fat replacement of the pancreas: case report and review of the literature. , 1996, Journal belge de radiologie.

[28]  A. Golay,et al.  Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. , 1987, The Journal of clinical endocrinology and metabolism.

[29]  B. Stamm.  Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. , 1984, Human pathology.

[30]  R. Unger.  Glucagon and insulin: a bihormonal system. , 1976, Comprehensive therapy.

[31]  L. Orci,et al.  THE ESSENTIAL ROLE OF GLUCAGON IN THE PATHOGENESIS OF DIABETES MELLITUS , 1975, The Lancet.