Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS) was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

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Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti‐malignant cell proliferation, anti‐inflammation, anti‐oxidation and liver protective effects. However, few studies have investigated SA’s antidepressant effects and pharmacological mechanisms of action. Our study aimed to explore the anti‐depression effect of SA and screen the target proteins regulated by SA in a rat model of chronic unpredictable mild stress (CUMS)‐induced depression. Results showed that 8‐week CUMS combined with separation could successfully produce depressive‐like behaviours and cause a decrease of dopamine (DA) in rat hippocampus, and 4‐week administration of SA could relieve CUMS rats’ depressive symptoms and up‐regulated DA content. There were 15 kinds of significant differentially expressed proteins that were detected not only between the control and CUMS groups, but also between the CUMS and SA treatment groups. Proline‐rich transmembrane protein 2 (PRRT2) was down‐regulated by CUMS while up‐regulated by SA. These findings reveal that SA may exert antidepressant effects by up‐regulating the expression level of PRRT2 and increasing DA content in hippocampus. The identification of these 15 differentially expressed proteins, including PRRT2, provides further insight into the treatment mechanism of SA for depression.

The objective of this study was to investigate the characteristics of blood glycemic excursion, incretins and pancreatic hormone secretion in elderly people with newly diagnosed type 2 diabetes mellitus (T2DM) and to study the effects of sitagliptin on glycemic excursion in these subjects. A total of 129 newly diagnosed T2DM patients were enrolled in the study from March 2012 to August 2013. Clinical data, serum incretin, pancreatic hormone and continuous glucose monitoring data were collected. Among these subjects, elderly patients (NEDM) randomly received metformin combined with sitagliptin phosphate or glimepiride for 24 weeks. The blood glucose, glycosylated hemoglobin A1c (GHbA1c), serum incretins and pancreatic hormone levels were determined. During the oral glucose tolerance test (OGTT), 30 min insulin and C-peptide levels, 120 min insulin levels and ratio of the increases of insulin and blood glucose levels after 30 min of sugar loading (∆Ins30/∆Glu30) were significantly lower in elderly patients than in middle-aged patients (P<0.05). In addition, the glucagon elevation at 30 min was higher and the glucagon-like peptide-1 (GLP-1) at 30 min was lower in the elderly patients (P<0.05). Glucose excursion indices, including the standard deviation of the average blood glucose, intraday mean average glucose excursions (MAGE), and mean of daily differences (MODD), were significantly higher in the elderly patients (P<0.05). During the OGTT, insulin, C-peptide and ∆Ins30/∆Glu30 results at 30 min and GLP-1 levels at 120 min in NEDM subjects were significantly increased (P<0.05) and glucagon levels at 30 min was significantly lower after sitagliptin treatment (P<0.05) compared with glimepiride. Moreover, MAGE and MODD were significantly lower in the sitagliptin group after treatment compared to those in the glimepiride group (P<0.05). No severe hypoglycemia or cardiovascular diseases were observed. Strong blood glucose excursions occur in elderly patients with newly diagnosed T2DM. Sitagliptin phosphate combined with metformin effectively and safely improves glycemic excursion and carbohydrate metabolism in NEDM patients by promoting the first phase of insulin and incretin secretion and inhibiting glucagon secretion of.

Cellular replacement therapy for diabetes mellitus (DM) has received much attention. In this study, we investigated the effect of transplantation of autologous bone marrow-derived mesenchymal stem cells (ABMSCs) in streptozotocin (STZ)-induced diabetic miniature pigs. Miniature pig BMSCs were cultured, labeled with superparamagnetic iron oxide (SPIO) and transplanted into the pancreas of diabetic miniature pigs through targeted intervention. Blood glucose levels, intravenous and oral glucose tolerance test (OGTT), serum insulin, C-peptide and islets histology were analyzed. These transplanted cells were then identified by magnetic resonance imaging (MRI). The results showed that transplantation of ABMSCs reversed STZ-induced diabetes in miniature pigs. Blood glucose levels, intravenous, OGTT, serum insulin and C-peptide were significantly recovered in the diabetic minipigs with the autologous BMSC (DMAB) transplantation group. In addition, the number of islets was significantly increased in this group compared to the diabetic minipig control (DMC) group with conventional therapy. These data suggested the implantation of autologous BMSCs for type 1 diabetes treatment can partially restore the function of islet β cells and maintain blood glucose homeostasis. Transplanted autologous BMSCs may improve islet repairing by differentiating for new islets and change pancreatic microcirculation and be identified in a real-time manner using MRI in vivo.

BackgroundAdefovir dipivoxil (ADV)-induced renal tubular dysfunction and hypophosphatemic osteomalacia (HO) have been given great consideration in the past few years. However, no standard guidance is available due to a lack of powerful evidence from appropriate long-term prospective case-control studies and variations in the definition of renal adverse events. The aim of this study is to clarify clinical features of ADV-related HO in Chinese chronic hepatitis B patients with long-term ADV treatment in Chinese and non-Chinese comparative case series.MethodsRetrieval of case reports was based on Pubmed, CNKI, Wan Fang and VIP databases using the key words adefovir dipivoxil, hypophosphatemia, osteomalacia and Fanconi syndrome. We divided patients into Chinese (C group) and Foreign (F group) groups according to their nationality. Comparisons involving demographics, clinical manifestations, tests, treatment and prognosis were conducted between the two groups.ResultsOf the patients screened, 120 Chinese patients were identified in the C group, and 32 non-Chinese patients were identified in the F group. The average age of the C group was younger than that of the F group (51.89 years ±10.96 years versus 56.47 years ±11.36 years, t = − 2.084, P = 0.039). No significant difference was found in gender (male to female, 3.29:1 versus 3:1, χ2 = 0.039, P = 0.844). Although there was no significant difference in the duration of ADV therapy before ostalgia onset, the C group tended to develop adverse events earlier, by 2–3 years, while the F group developed adverse events at 4–5 years (Z = − 1.517, P = 0.129). Prognosis was good after adjustment of the ADV dose and supplemental administration of phosphate and calcitriol. Time to resolution of tubular dysfunction was commenced at the first month, and Chinese patients were more prone to recover in the first 3 months than non-Chinese patients (91.3% of patients in the C group versus 56.3% in the F group, Z = − 3.013, P = 0.003).ConclusionsSufficient attention is required for middle-aged males before and during exposure to long-term ADV therapy, regardless of nationality. The clinical picture, laboratory and radiograph alterations are important clues for those patients and are usually characterized by polyarthralgia, renal tubular dysfunction and mineralization defects. Implementation of an early renal tubular injury index is recommended for patients with higher risk, which would prevent further renal injury.

Background Little is known about whether the influence of glycemic variability on arrhythmia is related to age in type 2 diabetes mellitus (T2DM). Therefore, we aimed to compare the association between glycemic variability and arrhythmia in middle-aged and elderly T2DM patients. Methods A total of 107 patients were divided into two groups: elderly diabetes mellitus group (EDM, n = 73) and middle-aged diabetes mellitus group (MDM, n = 34). The main clinical data, continuous glucose monitoring (CGM) and dynamic ECG reports were collected. The parameters including standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), time in range (TIR), time below range (TBR), time above range (TAR), coefficient of variation (CV) were tested for glycemic variability evaluation. Results In terms of blood glucose fluctuations, MAGE (5.77 ± 2.16 mmol/L vs 4.63 ± 1.89 mmol/L, P = 0.026), SDBG (2.39 ± 1.00 mmol/L vs 2.00 ± 0.82 mmol/L, P = 0.048), LAGE (9.53 ± 3.37 mmol/L vs 7.84 ± 2.64 mmol/L, P = 0.011) was significantly higher in EDM group than those of MDM group. The incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat were significantly higher in EDM group compared with the MDM group (all P < 0.05). Among patients with hypoglycemia events, the incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat (all P < 0.05) were significantly higher in the EDM group than those in the MDM group. In EDM group, TIR was negatively correlated with atrial tachycardia in the MAGE1 layer and with atrial tachycardia and ventricular premature beat in the MAGE2 layer, TBR was significantly positively correlated with atrial tachycardia in the MAGE2 layer (all P < 0.05). In MDM group, TAR was positively correlated with ventricular premature beat and atrial tachycardia in the MAGE2 layer (all P < 0.05). Conclusions The study demonstrated the elderly patients had greater glycemic variability and were more prone to arrhythmias. Therefore, active control of blood glucose fluctuation in elderly patients will help to reduce the risk of severe arrhythmia.