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    • Elevated DPP activity has been strongly

    2021-05-05

    Elevated DPP-4 activity has been strongly associated with diabetes mellitus, IR (Röhrborn et al., 2015), metabolic syndrome (Lamers et al., 2011) and inflammation (Zhong et al., 2015). However, report has it that GC exposure increases DPP-4activity in thymocyte homogenates (Kraml et al., 2003) but to the best of our knowledge, this is the first study that report elevated DPP-4 activity in GC-exposed rats during late pregnancy. However, one of the most remarkable findings from this study is that gestational GC exposure in female rats caused elevated DPP-4 activity suggesting that the glucose dysregulation induced by gestational GC exposure is DPP-4 dependent in female rats. Glycogen synthase kinase-3 (GSK-3), a multi-tasking and housekeeping enzyme that has widespread influences on many cellular functions, plays an important role in energy metabolism, however, it is constitutively active in resting Chaetocin (Guo et al., 2016). It constitutes part of the insulin signalling pathway and has been reported to be involved in the pathogenesis of IR and diabetes mellitus (Nikoulina et al., 2000). Nevertheless, there has been conflicting documents on the role of GSK-3 in GC-induced IR. There are reports that GC-induced IR can either be associated or not associated with GSK-3 (Ruzzin et al., 2005; Vaughan et al., 2015) although GC has been reported to induce pancreatic β-cell apoptosis through GSK-3-dependent pathway that was accompanied by oxidative stress (Guo et al., 2016). Another study showed that GSK-3 is involved in oxidative stress-induced GC insensitivity in chronic obstructive pulmonary disease patients (Ngkelo et al., 2015). Furthermore, the role of GSK-3 in the pathogenesis of inflammation has been widely documented as it accompanies inflammatory conditions such as diabetes mellitus, mood disorders, Alzheimer’s disease, cancer (Jope et al., 2007), and has been associated with atherothrombotic CVD events. However, another interesting finding in this study is that gestational GC exposure in rats decreases GSK-3 which is contrary to our previous finding where nicotine-/or COC-treatment in female rats led to increased GSK-3 accompanied with glucose deregulation and elevated circulating GC. In the same study, decreased GSK-3 was associated with improved gluco-metabolic function (Michael and Olatunji, 2017). Therefore, the finding of the current study suggest that the development of gluco-metabolic dysfunction in this animal model of gestational GC-induced IR is through GSK-3-independent but endoglin-/DPP-4-dependent pathway in female rats.
    Conclusions
    Conflict of interest
    Acknowledgments This research was supported by International Society of Hypertension (ISH) grant for mentors (2017) and Association of African Universities (AAU; 2017).
    Introduction Standard treatment for hypoglycemia is administration of dextrose but it is often insufficient when the hypoglycemia is caused by insulin secretagogues. In sulfonylurea-induced hypoglycemia, there is even a possibility that administered dextrose stimulates insulin secretion and prolongs hyperinsulinemia, resulting in recurrent hypoglycemia [1], [2]. When patients are treated with incretin-based therapy, insulin secretion by the dextrose could be further enhanced, because of the glucose-dependent nature of incretin actions.
    Case report A 77-year-old Japanese man with type 2 diabetes mellitus was presented to the emergency department of our hospital in an unconscious state. Type 2 diabetes had been diagnosed at age 60, and was treated with a DPP-4 inhibitor, vildagliptin, at a dose of 50mg twice a day. His recent HbA1c was 6.3% (44mmol/mol). He had chronic renal failure with an estimated glomerular filtration rate of 18.7mL/min/1.73m2. On arrival, the laboratory results included a blood glucose of 2.2mmol/L and creatinine of 238.7μmol/L. He was diagnosed as being in a hypoglycemic coma, and was treated with a 60mL intravenous infusion of 50% dextrose which restored consciousness. Two hours later, he again lost consciousness. He was promptly treated with a 50% dextrose infusion. Blood drawn at the same time showed a glucose concentration to be 2.4mmol/L and immunoreactive insulin (IRI) to be 318.8pmol/L. Thirty minutes later, blood glucose had increased to 4.6mmol/L however IRI also rose to 605.9pmol/L, leading to hypoglycemia (Fig. 1). A continuous infusion of 5% dextrose was started, but recurrent hypoglycemia continued. He required a central line for infusing high concentrations of dextrose. Despite continuous infusion of the dextrose, the patient continued to have recurrent hypoglycemia.