Low-level insulin content within abundant non-β islet endocrine cells in long-standing type 1 diabetes

CJ Lam, A Chatterjee, E Shen, AR Cox, JA Kushner - Diabetes, 2019 - Am Diabetes Assoc
CJ Lam, A Chatterjee, E Shen, AR Cox, JA Kushner
Diabetes, 2019Am Diabetes Assoc
Although most patients with type 1 diabetes (T1D) continue to produce small amounts of
insulin decades after disease onset, very few β-cells persist within their pancreata.
Consequently, the source of persistent insulin secretion within T1D remains unclear. We
hypothesized that low-level insulin content within non-β-cells could underlie persistent T1D
insulin secretion. We tested for low levels of insulin (insulinlow) within a large cohort of
JDRF Network for Pancreatic Organ Donors With Diabetes (nPOD) human pancreata across …
Although most patients with type 1 diabetes (T1D) continue to produce small amounts of insulin decades after disease onset, very few β-cells persist within their pancreata. Consequently, the source of persistent insulin secretion within T1D remains unclear. We hypothesized that low-level insulin content within non-β-cells could underlie persistent T1D insulin secretion. We tested for low levels of insulin (insulinlow) within a large cohort of JDRF Network for Pancreatic Organ Donors With Diabetes (nPOD) human pancreata across a wide range of ages and T1D disease durations. Long exposures, high-throughput imaging, and blinded parallel examiners allowed precise quantification of insulinlow cells. Of note, abundant islet endocrine cells with low quantities of insulin were present in most T1D pancreata. Insulinlow islet abundance and composition were not influenced by age, duration of diabetes, or age of onset. Insulinlow islets also contained β-cell markers at variable levels, including Pdx1, Nkx6.1, GLUT1, and PC1/3. Most insulinlow cells contained abundant glucagon and other α-cell markers, suggesting that α-cells drive much of the insulinlow phenotype in T1D. However, pancreatic polypeptide, somatostatin, and ghrelin cells also contributed to the insulinlow cell population. Insulinlow cells represent a potential source of persistent insulin secretion in long-standing T1D and a possible target for regenerative therapies to expand β-cell function in disease.
Am Diabetes Assoc