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Bariatric surgery is associated with a high remission rate of type 2 diabetes mellitus. However, it is unclear whether patients showing remission of diabetes actually have normal blood glucose levels throughout the day. We therefore performed continuous glucose monitoring (CGM) in 15 ambulatory patients showing remission of diabetes after laparoscopic sleeve gastrectomy (LSG) without or with duodenojejunal bypass (DJB) at the time of diabetic remission (12.9 ± 1.8 months after bariatric surgery). The definition of remission of diabetes was based on the American Diabetes Association criteria. The mean, SD, and coefficient of variation (CV) of glucose calculated from CGM were 6.2 ± 0.6 mmol/L, 1.5 ± 0.4 mmol/L, and 23.7 ± 6.2%, respectively. These values were higher than those of healthy participants without diabetes previously reported. The percentages of time spent above 10.0 mmol/L and below 3.9 mmol/L were 2.6 (IQR 0-5.0)% and 0 (IQR 0-8.0)%, respectively. Thus, patients with remission of diabetes after LSG or LSG/DJB still had substantial periods of hyperglycemia and hypoglycemia throughout the day. Therefore, we must manage patients with diabetes carefully, even after apparent remission of type 2 diabetes in response to bariatric surgery.

Aims Evaluation of the retinal microcirculation is key to understanding retinal vasculopathies, such as diabetic retinopathy. Laser speckle flowgraphy (LSFG) has recently enabled us to directly evaluate the vascular resistance in both retinal vessels and capillaries, non-invasively. We therefore assessed whether retinal vessel blood flow and/or the capillary microcirculation are associated with blood flow in the cervical arteries in diabetic patients without severe retinopathy. Methods We enrolled 110 type 2 diabetes patients, with no or mild non-proliferative diabetic retinopathy, in this prospective cross-sectional study. We measured the resistivity indices (RIs) of the retinal vessel and capillaries by LSFG and those of cervical arteries by Doppler ultrasonography, followed by analyzing associations. Results The RIs of not only the carotid but also vertebral arteries were associated with those of retinal vessel blood flow and the retinal capillary microcirculation. Multiple regression analyses revealed these associations to be independent of other explanatory variables including age and diabetes duration. Conclusions We obtained novel and direct evidence demonstrating a close association between the retinal microcirculation and cervical artery hemodynamics in diabetic patients. These findings suggest shared mechanisms to underlie micro- and macro-angiopathies. Thus, high vascular resistance of cervical arteries may be a risk of developing retinopathy.

Major symptoms of diabetes mellitus manifest, once pancreatic β-cell numbers have become inadequate. Although natural regeneration of β-cells after injury is very limited, bone marrow (BM) transplantation (BMT) promotes their regeneration through undetermined mechanism(s) involving inter-cellular (BM cell-to-β-cell) crosstalk. We found that two microRNAs (miRNAs) contribute to BMT-induced β-cell regeneration. Screening murine miRNAs in serum exosomes after BMT revealed 42 miRNAs to be increased. Two of these miRNAs (miR-106b-5p and miR-222-3p) were shown to be secreted by BM cells and increased in pancreatic islet cells after BMT. Treatment with the corresponding anti-miRNAs inhibited BMT-induced β-cell regeneration. Furthermore, intravenous administration of the corresponding miRNA mimics promoted post-injury β-cell proliferation through Cip/Kip family down-regulation, thereby ameliorating hyperglycemia in mice with insulin-deficient diabetes. Thus, these identified miRNAs may lead to the development of therapeutic strategies for diabetes., Graphical Abstract miR-106b-5p and miR-222-3p contribute to post-injury β-cell proliferation through down-regulation of Cip/Kip family members (p21Cip1and p27Kip1).Image 1, Highlights • BMT regenerates β-cells in mice with STZ-induced diabetes and increases miR-106b and miR-222 in serum exosomes and islets. • Inhibition with anti-miRs against these miRs suppresses BMT-induced β-cell regeneration. • Injection of miR-106b and miR-222 mimics promotes β-cell proliferation and improves hyperglycemia in STZ-treated mice. Regeneration of pancreatic β-cells is a promising therapeutic strategy not only for type 1 diabetes but also for certain forms of type 2 diabetes. However, natural regeneration of β-cells hardly ever occurs. Interestingly, bone marrow transplantation (BMT) has been shown to promote β-cell regeneration through an undetermined mechanism(s). In this study, we found that two microRNAs (miR-106b/-222) contribute to BMT-induced β-cell proliferation. Inhibition of miR-106b/-222 using specific anti-miRNAs significantly suppressed BMT-induced β-cell proliferation. Furthermore, intravenously administered miR-106b/222 promoted β-cell proliferation, thereby ameliorating hyperglycemia in mice with insulin-deficient diabetes. Thus, these identified miRNAs may lead to novel therapeutic strategies for diabetes.

Leptin resistance is an important mechanism underlying the development and maintenance of obesity and is thus regarded as a promising target of obesity treatment. Plasminogen activator inhibitor 1 (PAI-1), a physiological inhibitor of tissue-type and urokinase-type plasminogen activators, is produced at high levels in adipose tissue, especially in states of obesity, and is considered to primarily be involved in thrombosis. PAI-1 may also have roles in inter-organ tissue communications regulating body weight, because PAI-1 knockout mice reportedly exhibit resistance to high fat diet (HFD)-induced obesity. However, the role of PAI-1 in body weight regulation and the underlying mechanisms have not been fully elucidated. We herein studied how PAI-1 affects systemic energy metabolism. We examined body weight and food intake of PAI-1 knockout mice fed normal chow or HFD. We also examined the effects of pharmacological inhibition of PAI-1 activity by a small molecular weight compound, TM5441, on body weight, leptin sensitivities, and expressions of thermogenesis-related genes in brown adipose tissue (BAT) of HFD-fed wild type (WT) mice. Neither body weight gain nor food intake was reduced in PAI-1 KO mice under chow fed conditions. On the other hand, under HFD feeding conditions, food intake was decreased in PAI-1 KO as compared with WT mice (HFD-WT mice 3.98 ± 0.08 g/day vs HFD-KO mice 3.73 ± 0.07 g/day, P = 0.021), leading to an eventual significant suppression of weight gain (HFD-WT mice 40.3 ± 1.68 g vs HFD-KO mice 34.6 ± 1.84 g, P = 0.039). Additionally, TM5441 treatment of WT mice pre-fed the HFD resulted in a marked suppression of body weight gain in a PAI-1-dependent manner (HFD-WT-Control mice 37.6 ± 1.07 g vs HFD-WT-TM5441 mice 33.8 ± 0.97 g, P = 0.017). TM5441 treatment alleviated HFD-induced systemic and hypothalamic leptin resistance, before suppression of weight gain was evident. Moreover, improved leptin sensitivity in response to TM5441 treatment was accompanied by increased expressions of thermogenesis-related genes such as uncoupling protein 1 in BAT (HFD-WT-Control mice 1.00 ± 0.07 vs HFD-WT-TM5441 mice 1.32 ± 0.05, P = 0.002). These results suggest that PAI-1 plays a causative role in body weight gain under HFD-fed conditions by inducing hypothalamic leptin resistance. Furthermore, they indicate that pharmacological inhibition of PAI-1 activity is a potential strategy for alleviating diet-induced leptin resistance in obese subjects.

Communications services and traffic have become varied with the development of communications and progress in telecommunications network control for call acceptance and routing has been desired. In implementing flexible control in communications networks, which are complicated systems, introduction of fuzzy control techniques which is an application of knowledge engineering is considered to be effective. To realize fuzzy control efficiently, it is necessary to establish appropriately membership functions that are quantitatively homologous with the target of control. However, finding and identifying such membership functions are difficult tasks. From this viewpoint, this paper proposes a method of tuning a membership function by learning and investigates call acceptance control in detail as an example. By this method, the input values to the fuzzy system and the revenues of the network are measured and optimal values are obtained automatically for various parameters of the membership functions by learning based on these data and the past tuning history. In this study, the efficiency of this tuning method is evaluated by simulation. As a result, it has been shown that by this method membership functions converge to appropriate forms and good control characteristics can be obtained.

In the ATM switching system, various kinds of information are multiplexed and transferred. Thus, priority control is required to satisfy various qualities. This paper proposes a cell transfer ratio control-type priority control method in which a buffer is prepared for each quality class and the maximum number of continuously transferrable cells is defined for each class when sending cells from the buffer. Required transmission quality is realized by the class ratio (cell transfer ratio) and the buffer size. The multiqueue system controlled by this method is analyzed and traffic characteristics such as mean waiting time and cell loss probability at the buffer are evaluated. As a result, the effectiveness of the quality control with the proposed method is shown.