Moin, Abu Saleh Md

AbstractIntroductionWe sought to determine whether chromogranin A‐positive hormone‐negative (CPHN) endocrine cells are increased in the pancreas of pregnant women, offering potential evidence in support of neogenesis.MethodsAutopsy pancreata from pregnant women (n = 14) and age‐matched non‐pregnant control women (n = 9) were obtained. Staining of pancreatic sections for chromogranin A, insulin and a cocktail of glucagon, somatostatin, pancreatic polypeptide and ghrelin was undertaken, with subsequent evaluation for CPHN cell frequency.ResultsThe frequency of clustered β‐cells was increased in pregnant compared to non‐pregnant subjects (46.6 ± 5.0 vs. 31.8 ± 5.0% clustered β‐cells of total clustered endocrine cells, pregnant vs. non‐pregnant, p < .05). Frequency of endocrine cocktail cells was lower in pregnant women than non‐pregnant women (36.2 ± 4.0 vs. 57.0 ± 6.8% clustered endocrine cocktail cells of total clustered endocrine cells, pregnant vs. non‐pregnant, p < .01). No difference in frequency of CPHN cells was found in islets, nor in clustered or single cells scattered throughout the exocrine pancreas, between pregnant and non‐pregnant women. The frequency of CPHN cells in pregnancy was independent of the number of pregnancies (gravidity).ConclusionsOur findings of no increase in CPHN cell frequency in pancreas of pregnant women suggest that this potential β‐cell regenerative mechanism is not that by which the increased β‐cell mass of pregnancy is achieved. However, an increase in the percentage of clustered β‐cells was found in pregnancy, with decreased frequency of other endocrine cells in clusters, suggesting a compensatory shift from other pancreatic endocrine cell types to β‐cells as a mechanism to meet the increased insulin demands of pregnancy.

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 to 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 were 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 ~190 mg 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.

AbstractContextChronic pancreatitis (CP) is characterized by inflammation, fibrosis, and a loss of pancreatic acinar cells, which can result in exocrine and eventually endocrine deficiency. Pancreatitis has been reported to induce formation of new endocrine cells (neogenesis) in mice. Our recent data have implicated chromogranin A–positive hormone-negative (CPHN) cells as potential evidence of neogenesis in humans.ObjectiveWe sought to establish if CPHN cells were more abundant in CP in humans.Design, Setting, and ParticipantsWe investigated the frequency and distribution of CPHN cells and the expression of the chemokine C-X-C motif ligand 10 (CXCL10) and its receptor chemokine C-X-C motif receptor 3 in pancreas of nondiabetic subjects with CP.ResultsCPHN cell frequency in islets was increased sevenfold in CP [2.1% ± 0.67% vs 0.35% ± 0.09% CPHN cells in islets, CP vs nonpancreatitis (NP), P &lt; 0.01], as were the CPHN cells found as scattered cells in the exocrine areas (17.4 ± 2.9 vs 4.2 ± 0.6, CP vs NP, P &lt; 0.001). Polyhormonal endocrine cells were also increased in CP (2.7 ± 1.2 vs 0.1 ± 0.04, CP vs NP, % of polyhormonal cells of total endocrine cells, P &lt; 0.01), as was expression of CXCL10 in α and β cells.ConclusionThere is increased islet endogenous expression of the inflammation marker CXCL10 in islets in the setting of nondiabetic CP and an increase in polyhormonal (insulin-glucagon expressing) cells. The increase in CPHN cells in CP, often in a lobular distribution, may indicate foci of attempted endocrine cell regeneration.