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Key Clinical Message: Primary hyperaldosteronism with type 3 autoimmune polyendocrine syndrome was a rare combination of both hyper‐ and hypoendocrine gland function. Comprehensive treatment including surgery and replacement therapy might be an effective strategy. Primary aldosteronism (PA) is a common cause of secondary hypertension originating from hormones. Type 3 autoimmune polyendocrine syndrome (APS‐3) is characterized by the simultaneous or subsequent occurrence of autoimmune‐mediated endocrine gland damage, except for Addison disease. Here we reported an extremely rare case of a 63‐year‐old woman with PA and APS‐3 who initially presented with hypertension (HT). The APS‐3 of this patient mainly exhibited type 1 diabetes mellitus (T1DM) and Hashimoto's thyroiditis. She underwent the adrenal adenoma resection with a histopathologic diagnosis of adrenal cortical adenoma. After surgery, the HT of this patient was immediately reversed, and the concentration of serum potassium went back to normal. Then, this patient was administered with replacement therapy of insulin and levothyroxine sodium tablets (L‐T4). [ABSTRACT FROM AUTHOR]

Aims: To investigate whether treatment with γ-aminobutyric acid (GABA) alone or in combination with glucagon receptor (GCGR) monoclonal antibody (mAb) exerted beneficial effects on β-cell mass and α-cell mass, and to explore the origins of the regenerated β-cells in mice with type 1 diabetes (T1D). Methods: Streptozotocin (STZ)-induced T1D mice were treated with intraperitoneal injection of GABA (250 μg/kg per day) and/or REMD 2.59 (a GCGR mAb, 5 mg/kg per week), or IgG dissolved in PBS for 8 weeks. Plasma hormone levels and islet cell morphology were evaluated by ELISA and immunofluorescence, respectively. The origins of the regenerated β-cells were analyzed by double-immunostaining, α-cell lineage-tracing and BrdU-tracing studies. Results: After the 8-week treatment, GABA or GCGR mAb alone or in combination ameliorated hyperglycemia in STZ-induced T1D mice. GCGR mAb upregulated plasma insulin level and increased β-cell mass, and GABA appeared to have similar effects in T1D mice. However, combination treatment did not reveal any additive or synergistic effect. Interestingly, the GCGR mAb-induced increment of plasma glucagon level and α-cell mass was attenuated by the combined treatment of GABA. In addition, duct-derived β-cell neogenesis and α-to-β cell conversion but not β-cell proliferation contributed to the increased β-cell mass in T1D mice. Conclusion: These results suggested that GABA attenuated α-cell hyperplasia but did not potentiates β-cell regeneration induced by GCGR mAb in T1D mice. Our findings provide novel insights into a combination treatment strategy for β-cell regeneration in T1D. [ABSTRACT FROM AUTHOR]

Pancreatic β-cell neogenesis in vivo holds great promise for cell replacement therapy in diabetic patients, and discovering the relevant clinical therapeutic strategies would push it forward to clinical application. Liraglutide, a widely used antidiabetic glucagon-like peptide-1 (GLP-1) analog, has displayed diverse β-cell-protective effects in type 2 diabetic animals. Glucagon receptor (GCGR) monoclonal antibody (mAb), a preclinical agent that blocks glucagon pathway, can promote recovery of functional β-cell mass in type 1 diabetic mice. Here, we conducted a 4-week treatment of the two drugs alone or in combination in type 1 diabetic mice. Although liraglutide neither lowered the blood glucose level nor increased the plasma insulin level, the immunostaining showed that liraglutide expanded β-cell mass through self-replication, differentiation from precursor cells, and transdifferentiation from pancreatic α cells to β cells. The pancreatic β-cell mass increased more significantly after GCGR mAb treatment, while the combination group did not further increase the pancreatic β-cell area. However, compared with the GCGR mAb group, the combined treatment reduced the plasma glucagon level and increased the proportion of β cells/α cells. Our study evaluated the effect of liraglutide, GCGR mAb monotherapy, or combined strategy in glucose control and islet β-cell regeneration and provided useful clues for the future clinical application in type 1 diabetes. [ABSTRACT FROM AUTHOR]