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Sulfonylurea Therapy in Neonatal Diabetes: Impact on KATP Channel-Related Remission

This study explores the role of acute sulfonylurea therapy in patients with KATP-induced neonatal diabetes. It highlights the potential for permanent remission upon disease onset, particularly in cases with mutations in the KCNJ11 and ABCC8 genes. The findings demonstrate that sulfonylureas positively influence insulin secretion and ATP/ADP ratios, leading to varied outcomes in glucose metabolism and β-cell function. The research emphasizes the need for tailored management in neonatal diabetes to harness the benefits of sulfonylurea therapy and prevent hyperglycemia.

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Sulfonylurea Therapy in Neonatal Diabetes: Impact on KATP Channel-Related Remission

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  1. Acute Sulfonylurea therapy at disease onset can cause permanent remission of KATP-induced diabetesRemedi MS et al. Diabetes. 2011; 60:2515-2522

  2. Healthy Neonatal Diabetes High Glucose Ca2+ • Mutations: • KCNJ11 • - ABCC8 (SUR1) Kir6.2 SUR1 Depolarization Insulin Secretion ATP K+ High ATP/ADP ratio

  3. Healthy Neonatal Diabetes Sulfonylureas High Glucose Ca2+ • Mutations: • KCNJ11 • - ABCC8 (SUR1) Kir6.2 SUR1 Depolarization Different outcomes Insulin Secretion ATP K+ High ATP/ADP ratio

  4. Healthy Neonatal Diabetes Sulfonylureas High Glucose Ca2+ • Mutations: • KCNJ11 • - ABCC8 (SUR1) Kir6.2 SUR1 Depolarization Different outcomes Insulin Secretion ATP K+ High ATP/ADP ratio Mouse neonate • KATP dependent neonatal diabetes • Hyperglycemia • Loss of β-cells

  5. Healthy Neonatal Diabetes Sulfonylureas High Glucose Ca2+ • Mutations: • KCNJ11 • - ABCC8 (SUR1) Kir6.2 SUR1 Depolarization Different outcomes Insulin Secretion ATP K+ High ATP/ADP ratio Mouse neonate Sulfonylureas 6 days • KATP dependent neonatal diabetes • Hyperglycemia • Loss of β-cells Early onset of neonatal diabetes

  6. Healthy Neonatal Diabetes Sulfonylureas High Glucose Ca2+ • Mutations: • KCNJ11 • - ABCC8 (SUR1) Kir6.2 SUR1 Depolarization Different outcomes Sulfonylureas Insulin Secretion Not cured (70%) ATP K+ High ATP/ADP ratio Cured (30%) Fed Glucose Mouse neonate Sulfonylureas time 6 days • KATP dependent neonatal diabetes • Hyperglycemia • Loss of β-cells Early onset of neonatal diabetes Insulin Content Not Cured Cured

  7. Healthy Neonatal Diabetes Sulfonylureas High Glucose Ca2+ • Mutations: • KCNJ11 • - ABCC8 (SUR1) Kir6.2 SUR1 Depolarization Different outcomes Sulfonylureas Insulin Secretion Not cured (70%) ATP K+ High ATP/ADP ratio Cured (30%) Fed Glucose Mouse neonate Sulfonylureas time 6 days • KATP dependent neonatal diabetes • Hyperglycemia • Loss of β-cells Early onset of neonatal diabetes Insulin Content Not Cured Cured

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