Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production

© 2018 The Author(s). Published by Elsevier Inc.Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in α cells from hyperglycemic Fh1βKO and β-V59M gain-of-function KATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1βKO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.Peer reviewe

Design, management and completion of the hypoCOMPaSS RCT evaluating potential for restoration of hypoglycaemia awareness in type 1 diabetes using conventional vs novel technologie : and exploration of potential phenotypes predicting persistent impaired awareness despite study intervention

M.DAim: To explore the extent to which impaired awareness of hypoglycaemia (IAH) can be improved using currently available treatment regimens in individuals with long-standing type 1 diabetes mellitus (T1DM), and to characterise those individuals whose awareness of hypoglycaemia did not improve. Methods: A multicentre, 2x2 factorial 24-week RCT (HypoCOMPaSS) comparing multiple daily injections (MDI) and continuous subcutaneous insulin infusion therapy (CSII) with or without real-time continuous glucose monitoring (RT) in a population with T1DM and IAH was designed. The study was undertaken in five UK centres using established and novel outcome measures to assess hypoglycaemia awareness, glycaemic control and treatment satisfaction. A second analysis was undertaken characterising individuals within the HypoCOMPaSS population as responders and non-responders. Complication status, autonomic symptom profile and hyperglycaemia avoidance scores were assessed. Results: Overall, hypoglycaemia awareness improved, and biochemical hypoglycaemia, severe hypoglycaemia rate and insulin doses reduced without deterioration in HbA1c. There were no significant differences in awareness comparing MDI with CSII; and RT with conventional glucose monitoring. Between-group analyses demonstrated comparable reductions in severe hypoglycaemia, biochemical hypoglycaemia, fear of hypoglycaemia and insulin doses with equivalent HbA1c. Treatment satisfaction was highest with CSII. In the second study there was a suggestion that longer diabetes duration and increased age may impair ability to respond to the interventions but this did not correlate with severity of autonomic symptoms. Conclusions: Hypoglycaemia awareness can be improved and recurrent severe hypoglycaemia prevented in long-standing T1DM without relaxing HbA1c. Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII / RT. All individuals may benefit from biomedical interventions to improve awareness of hypoglycaemia. This ii research provides a basis for further studies investigating impact of new technologies on severe hypoglycaemia and underlines the importance of tailoring treatment to avoid biochemical hypoglycaemia without relaxing overall control

The cells of the islets of Langerhans

Islets of Langerhans are islands of endocrine cells scattered throughout the pancreas. A number of new studies have pointed to the potential for conversion of non-β islet cells in to insulin-producing β-cells to replenish β-cell mass as a means to treat diabetes. Understanding normal islet cell mass and function is important to help advance such treatment modalities: what should be the target islet/β-cell mass, does islet architecture matter to energy homeostasis, and what may happen if we lose a particular population of islet cells in favour of β-cells? These are all questions to which we will need answers for islet replacement therapy by transdifferentiation of non-β islet cells to be a reality in humans. We know a fair amount about the biology of β-cells but not quite as much about the other islet cell types. Until recently, we have not had a good grasp of islet mass and distribution in the human pancreas. In this review, we will look at current data on islet cells, focussing more on non-β cells, and on human pancreatic islet mass and distribution

PENYULUHAN MENGENAL HIPOGLIKEMIA DAN PENANGANANNYA SECARA DARING

Hipoglikemia adalah kondisi ketika kadar glukosa (gula darah) berada di bawah normal. Umumnya, seseorang dianggap mengalami hipoglikemia saat kadar gula darahnya kurang dari 70 mg/dl. Kadar glukosa darah terlalu rendah akan membahayakan tubuh karena dapat merusak jaringan otak. Artikel ini menguraikan tentang kegiatan pengabdian masyarakat dalam bentuk penyuluhan online yang bertujuan untuk mengedukasi siswa/i kelas X, Sekolah Menengah Atas (SMA) Taman Madya I Jakarta mengenai penyebab, gejala dan penanganan hipoglikemia. Metode yang digunakan berupa metode penyuluhan dan tanya jawab dengan alat bantu berupa poster infografis, slide power point (ppt). Kegiatan ini juga melibatkan peran serta mahasiswa/i dari peserta mata kuliah Biokimia sebagai bentuk implementasi materi perkuliahan pada masyarakat. Kegiatan ini bermanfaat untuk meningkatkan pengetahuan siswa/i SMA (kelas X) tentang hipoglikemia