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Abu Saleh Md Moin, Megan Cory, Tatyana Gurlo, Yoshifumi Saisho, Robert A Rizza, Peter C Butler and Alexandra E Butler

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.

Free access

Francesco S Celi, Robert J Brychta, Joyce D Linderman, Peter W Butler, Anna Teresa Alberobello, Sheila Smith, Amber B Courville, Edwin W Lai, Rene Costello, Monica C Skarulis, Gyorgy Csako, Alan Remaley, Karel Pacak and Kong Y Chen

Objective

Resting energy expenditure (EE) is a major contributor to the total EE and thus plays an important role in body weight regulation. Adaptive thermogenesis is a major component of EE in rodents, but little is known on the effects of exposure of humans to mild and sustainable reduction in environmental temperature.

Design

To characterize the dynamic changes in continuously measured resting EE, substrate utilization, and hormonal axes simultaneously in response to mild reduction in environmental temperature, we performed a cross-over intervention.

Methods

Twenty-five volunteers underwent two 12-h recordings of EE in whole room indirect calorimeters at 24 and 19 °C with simultaneous measurement of spontaneous movements and hormonal axes.

Results

Exposure to 19 °C resulted in an increase in plasma and urine norepinephrine levels (P<0.0001), and a 5.96% (P<0.001) increase in EE without significant changes in spontaneous physical activity. Exposure to the lower temperature resulted in a significant increase in free fatty acid levels (P<0.01), fasting insulin levels (P<0.05), and a marginal decrease in postprandial glucose levels. A small but significant (P<0.002) increase in serum free thyroxine and urinary free cortisol (P<0.05) was observed at 19 °C.

Conclusions

Our observations indicate that exposure to 19 °C, a mild and tolerable cold temperature, results in a predictable increase in EE driven by a sustained rise in catecholamine and the activation of counter-regulatory mechanisms.