地锦草水提液对糖尿病小鼠的降血糖作用

目的观察地锦草水提液对糖尿病小鼠的降血糖作用,并探究其作用机制。方法对60只小鼠进行尾静脉注射0.25%四氧嘧啶溶液80mg·kg-1,注射后2h给予50%葡萄糖溶液0.2mL·10g-1灌胃造模,3d后眼眶采血测血糖,血糖值〉11.1mmol·L-1为糖尿病小鼠。将50只造模成功的小鼠按随机数字表法分为5组：NS组（阴性对照组）,地锦草低（59mg·kg-1·d-1）、中（118mg·kg-1·d-1）、高（236mg·kg-1·d-1）剂量组,二甲双胍组（阳性对照组）,每组10只。连续给药14d后,观察地锦草水提液对糖尿病小鼠血糖、血清胰岛素、胰岛病理形态变化的影响。结果 1）备糖：地锦草高剂量组和二甲双胍组给药后的血糖明显低于给药前及NS组,地锦草低、中剂量组（均P〈0.05）,NS组、地锦草中、低剂量组血糖也略下降,但差异均无统计学意义（均P〉0.05）。2）血清胰岛素：地锦草高剂量组、二甲双胍组血清胰岛素水平均显著高于NS组及地锦草低、中剂量组（均P〈0.05）,地锦草低、中剂量组及NS组比较差异均无统计学意义（均P〉0.05）。3）胰腺的病理形态：NS组胰岛数量明显减少,结构破坏,边界模糊不清,胰岛β细胞排列紊乱,部分细胞出现变性或坏死;地锦草各剂量组胰岛数量较多,胰岛结构较完整,境界较清晰,胰岛β细胞排列较整齐,细胞形态较好,胞浆丰富,胞核多数清楚,仅可见少数细胞变性或坏死;二甲双胍组胰岛形态有一定的恢复。结论地锦草水提液对糖尿病小鼠的降血糖作用可能是通过保护胰岛β细胞、减轻其损伤及增加胰岛素分泌来实现。     

葛根煎剂对四氧嘧啶致糖尿病小鼠血糖及其并发症的影响

以四氧嘧啶致小鼠建立糖尿病模型,经葛根煎剂灌胃,连续35 d,每周测定空腹血糖和体重;小鼠在灌胃结束后,断头处死,分别取其胰腺和肾脏做切片进行检查.结果显示:葛根煎剂对糖尿病模型小鼠空腹血糖水平有一定的降低作用,但作用强度较弱;能改善小鼠体质的作用;对肾病并发症有较好的疗效,对被破坏的胰岛细胞有恢复和修复作用.     

New Insights in the Control of Fat Homeostasis: The Role of Neurotensin

Neurotensin (NT) is a small peptide with pleiotropic functions, exerting its primary actions by controlling food intake and energy balance. The first evidence of an involvement of NT in metabolism came from studies on the central nervous system and brain circuits, where NT acts as a neurotransmitter, producing different effects in relation to the specific region involved. Moreover, newer interesting chapters on peripheral NT and metabolism have emerged since the first studies on the NT-mediated regulation of gut lipid absorption and fat homeostasis. Intriguingly, NT enhances fat absorption from the gut lumen in the presence of food with a high fat content, and this action may explain the strong association between high circulating levels of pro-NT, the NT stable precursor, and the increased incidence of metabolic disorders, cardiovascular diseases, and cancer observed in large population studies. This review aims to provide a synthetic overview of the main regulatory effects of NT on several biological pathways, particularly those involving energy balance, and will focus on new evidence on the role of NT in controlling fat homeostasis, thus influencing the risk of unfavorable cardio–metabolic outcomes and overall mortality in humans.     

Hematopoietic Progenitors and the Bone Marrow Niche Shape the Inflammatory Response and Contribute to Chronic Disease

It is now well understood that the bone marrow (BM) compartment can sense systemic inflammatory signals and adapt through increased proliferation and lineage skewing. These coordinated and dynamic alterations in responding hematopoietic stem and progenitor cells (HSPCs), as well as in cells of the bone marrow niche, are increasingly viewed as key contributors to the inflammatory response. Growth factors, cytokines, metabolites, microbial products, and other signals can cause dysregulation across the entire hematopoietic hierarchy, leading to lineage-skewing and even long-term functional adaptations in bone marrow progenitor cells. These alterations may play a central role in the chronicity of disease as well as the links between many common chronic disorders. The possible existence of a form of “memory” in bone marrow progenitor cells is thought to contribute to innate immune responses via the generation of trained immunity (also called innate immune memory). These findings highlight how hematopoietic progenitors dynamically adapt to meet the demand for innate immune cells and how this adaptive response may be beneficial or detrimental depending on the context. In this review, we will discuss the role of bone marrow progenitor cells and their microenvironment in shaping the scope and scale of the immune response in health and disease.     

HNF1A Mutations and Beta Cell Dysfunction in Diabetes

Understanding the genetic factors of diabetes is essential for addressing the global increase in type 2 diabetes. HNF1A mutations cause a monogenic form of diabetes called maturity-onset diabetes of the young (MODY), and HNF1A single-nucleotide polymorphisms are associated with the development of type 2 diabetes. Numerous studies have been conducted, mainly using genetically modified mice, to explore the molecular basis for the development of diabetes caused by HNF1A mutations, and to reveal the roles of HNF1A in multiple organs, including insulin secretion from pancreatic beta cells, lipid metabolism and protein synthesis in the liver, and urinary glucose reabsorption in the kidneys. Recent studies using human stem cells that mimic MODY have provided new insights into beta cell dysfunction. In this article, we discuss the involvement of HNF1A in beta cell dysfunction by reviewing previous studies using genetically modified mice and recent findings in human stem cell-derived beta cells.     

Intracavernous Injection of Platelet-Rich Plasma Therapy Enhances Erectile Function and Decreases the Mortality Rate in Streptozotocin-Induced Diabetic Rats

Erectile dysfunction (ED) is an agonizing complication of diabetes mellitus (DM) and it is challenging to treat ED in DM patients. Platelet-rich plasma (PRP) is a unique therapeutic strategy comprising intrinsic growth factors. An attempt was made to explore the potentiality of the PRP treatment in DM-induced ED rats in various groups (control, DM-non-ED, DM-ED, and DM-ED treated with PRP). Streptozotocin (STZ) was used to induce DM in rats. The blood glucose levels of the DM rats were maintained at >300 mg/dl. In the 18-week experiment, survival rate, body weight, intracavernous pressure (ICP) variations, and arterial blood pressure were analyzed. The tissue restoration results were validated by histological, immunofluorescence, and transmission electron microscopic analysis. PRP treatment of DM-ED rats significantly increased all parameters of erectile function compared to pre-treatment of PRP and DM-ED treated with vehicle. The histological results revealed that PRP treatment substantially enhanced the regeneration of myelinated nerves and decreased the atrophy of corporal smooth muscle. Notably, the PRP treatment immensely enhanced the survival rate in post-surgery DM-ED rats. These results indicated certain benefits of PRP treatment in delaying damage and preventing post-surgery complications in DM patients. Hence, PRP treatment is a novel multifactorial strategy for DM-ED patients.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.