The release of GLP-1 from gut L cells is inhibited by low extracellular pH.

Objective: The intestinal luminal pH profile varies from stomach to rectum and becomes disrupted in diseases. However, little is known about the pH dependence of incretin hormone secretion, with most in vitro studies having failed to consider this modulatory factor or having used nonphysiological buffer systems. Here, we report the extracellular pH (pHe) dependence of glucagon-like peptide-1 (GLP-1) exocytosis from L cells.

Traditional Japanese medicine Kamikihito ameliorates sucrose preference, chronic inflammation and obesity induced by a high fat diet in middle-aged mice.

The high prevalence of obesity has become a pressing global public health problem and there exists a strong association between increased BMI and mortality at a BMI of 25 kg/m or higher. The prevalence of obesity is higher among middle-aged adults than among younger groups and the combination of aging and obesity exacerbate systemic inflammation. Increased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha (TNFα) are hallmarks of obesity, and promote the secretion of hepatic C-reactive protein (CRP) which further induces systematic inflammation.

Systemic Co-Administration of Low-Dose Oxytocin and Glucagon-Like Peptide 1 Additively Decreases Food Intake and Body Weight.

Introduction: GLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side effects, and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug.

Blood purification practices: Some ethnopharmacological insight from a rural community in KwaZulu-Natal, South Africa.

Ethnopharmacological Relevance: Blood purification practices, also referred to as blood cleansing or detoxification, is an ancient concept which is widespread within African traditional medicine. There is, however, limited consolidated information about the selection of plant species, the purpose of use and how the preparation is made. An in-depth examination of how regional communities use medicinal plants for blood purification is needed to better understand this ethnopharmacological practice.

NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells.

Type 2 diabetes mellitus (T2DM) remains one of the most pressing health issues facing modern society. Several antidiabetic drugs are currently in clinical use to treat hyperglycaemia, but there is a need for new treatments that effectively restore pancreatic islet function in patients. Recent studies reported that both murine and human pancreatic islets exhibit enhanced insulin release and β-cell viability in response to N-methyl-D-aspartate (NMDA) receptor antagonists.

Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion.

Dysregulated glucagon secretion from pancreatic alpha-cells is a key feature of type-1 and type-2 diabetes (T1D and T2D), yet our mechanistic understanding of alpha-cell function is underdeveloped relative to insulin-secreting beta-cells. Here we show that the enzyme acetyl-CoA-carboxylase 1 (ACC1), which couples glucose metabolism to lipogenesis, plays a key role in the regulation of glucagon secretion. Pharmacological inhibition of ACC1 in mouse islets or αTC9 cells impaired glucagon secretion at low glucose (1 mmol/l).

The use of African traditional medicines amongst Zulu women during childbearing in northern KwaZulu-Natal.

In Africa, some women are still heavily depending on traditional medicine during childbearing to maintain healthy pregnancy, postpartum recovery and for infant care. This study was designed to assess the prevalence of traditional medicine use and associated factors of its use during childbearing. Data were collected using structured questionnaires and individual interviews were conducted with 140 women.

Traditional food taboos and practices during pregnancy, postpartum recovery, and infant care of Zulu women in northern KwaZulu-Natal.

Background: Traditional practices and beliefs influence and support the behavior of women during pregnancy and childbirth in different parts of the world. Not much research has been conducted to examine whether and how cultural traditions continue to shape maternity experiences of Zulu women. The aim of this study is to establish the extent at which women in certain rural communities adhere to traditional food taboos and practices during pregnancy, postpartum recovery, and infants feeding, in comparison to what is recommended by health care workers.

Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1.

Objective: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown.

A Ketone Ester Drink Lowers Human Ghrelin and Appetite.

Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the effects of an exogenous ketone ester (KE) on appetite.

Perceived barriers and facilitators to HIV testing in South African communities.

We interviewed 15 South Africans seeking HIV testing to understand the factors that influenced their seeking an HIV test. Reasons in favour of testing included having had unprotected sex, availability of social support if testing HIV positive and modelling test-seeking behaviour to others. Reasons against seeking testing included fear testing HIV positive, the possibility of receiving treatment too late, HIV-related stigma and long distances to testing sites.

Plants used to treat skin diseases in northern Maputaland, South Africa: antimicrobial activity and in vitro permeability studies.

Context: Ethnobotanical claims of medicinal plants used in northern Maputaland are limited. Objectives To establish scientific validity for a selection of the plants used in Maputaland to treat skin diseases.

Materials And Methods: Aqueous and dichloromethane-methanol extracts were prepared from 37 plant species which were collected from four rural communities in Maputaland.

Carpal tunnel syndrome: The role of collagen gene variants.

Introduction: The direct causes of idiopathic carpal tunnel syndrome (CTS) are still unknown. It is suggested that pathology of the tendons and other connective tissue structures within the carpal tunnel may play a role in its aetiology. Variants in genes encoding connective tissue proteins, such as type V collagen, have previously been associated with CTS.

Matrix metalloproteinase genes on chromosome 11q22 and risk of carpal tunnel syndrome.

Involvement of tendons and/or connective tissue structures in the aetiology of idiopathic carpal tunnel syndrome (CTS) has been proposed. DNA sequence variants within genes encoding structural components of the collagen fibril, the basic structural unit of connective tissue, have been shown to associate with modulating CTS risk. The matrix metalloproteinases (MMPs) play an important role in connective tissue remodelling.

Molecular action of sulphonylureas on KATP channels: a real partnership between drugs and nucleotides.

Sulphonylureas stimulate insulin secretion from pancreatic β-cells primarily by closing ATP-sensitive K(+) channels in the β-cell plasma membrane. The mechanism of channel inhibition by these drugs is unusually complex. As direct inhibitors of channel activity, sulphonylureas act only as partial antagonists at therapeutic concentrations.

Antimicrobial evaluation of plants used for the treatment of diarrhoea in a rural community in northern Maputaland, KwaZulu-Natal, South Africa.

Background: Zulu people living in the rural area of Maputaland (KwaZulu-Natal, South Africa) rely heavily on medicinal plants for the treatment of diarrhoea. Abundant availability of medicinal plants in the study area offers low cost health care, but scientific validation is needed in order to lend credibility to the traditional use against many ailments including diarrhoeal infections. With this in mind a study was designed to test the in vitro antimicrobial efficacy of 23 plant species which are used for the treatment of diarrhoea in rural Maputaland.

Interleukin and growth factor gene variants and risk of carpal tunnel syndrome.

Recent research has identified DNA sequence variants within genes encoding structural components of the collagen fibril, the basic structural unit of tendons, to modify the risk of carpal tunnel syndrome (CTS). Since the expression of these previously associated genes are regulated by cytokine and growth factor signalling pathways, the aim of this study was to determine whether variants within these cell signalling pathway genes, namely interleukin 1β (IL-1β), IL-6, interleukin 6 receptor (IL-6R) and vascular endothelial growth factor A(VEGFA), are also associated with CTS. One hundred and three self-reported Coloured participants, with a history of carpal tunnel release surgery (CTS) and 149 matched control participants (CON) without any reported history of CTS symptoms were genotyped for the functional IL-1β rs16944 (-511C/T), IL-6 rs1800795 (-174G/C), IL-6R rs2228145 (C/A) and VEGFA rs699947 (-2578C/A) variants.

Sulfonylureas suppress the stimulatory action of Mg-nucleotides on Kir6.2/SUR1 but not Kir6.2/SUR2A KATP channels: a mechanistic study.

Sulfonylureas, which stimulate insulin secretion from pancreatic β-cells, are widely used to treat both type 2 diabetes and neonatal diabetes. These drugs mediate their effects by binding to the sulfonylurea receptor subunit (SUR) of the ATP-sensitive K(+) (KATP) channel and inducing channel closure. The mechanism of channel inhibition is unusually complex.

The BGN and ACAN genes and carpal tunnel syndrome.

The causes of idiopathic carpal tunnel syndrome (CTS) remain unknown and the involvement of the tendons within the carpal tunnel structure in the aetiology of CTS cannot be excluded. Variants within the COL5A1 gene, an important regulator of fibril assembly in tendons, have previously been associated with modulating the risk of CTS. Furthermore, proteoglycans are also important structural components of tendons and variants within the aggrecan gene are associated with musculoskeletal soft tissue injuries.

The COL5A1 gene is associated with increased risk of carpal tunnel syndrome.

The direct causes of idiopathic carpal tunnel syndrome (CTS), a common upper limb entrapment neuropathy, remain unknown. It is however generally accepted that an increase in pressure within the carpal tunnel structure, which contains nine flexor tendons, causes compression of the median nerve. The involvement of these tendons in the aetiology of CTS cannot be excluded.

Plants traditionally used individually and in combination to treat sexually transmitted infections in northern Maputaland, South Africa: antimicrobial activity and cytotoxicity.

Ethnopharmacological Relevance: Although medicinal plants are used extensively to treat sexually transmitted infections (STIs) in rural northern Maputaland, KwaZulu-Natal, the efficacy and safety of these plants have not previously been evaluated.

Aim Of Study: A study was designed to investigate the in vitro antimicrobial activity and cytotoxicity profiles of a selection (individual plants and selected combinations) of traditionally used plants in this study area.

Materials And Methods: Aqueous and organic (dichloromethane: methanol, 1:1) extracts were prepared.

Medicinal plants used for the treatment of various skin disorders by a rural community in northern Maputaland, South Africa.

Background: Skin diseases have been of major concern recently due to their association with the Human Immunodeficiency Virus and Acquired Immunity Deficiency Syndrome (HIV/AIDS). The study area (northern Maputaland) has the highest HIV infection rate in South Africa, which made them more prone to a wide range of skin conditions. Fungal infections due to the hot climate and overcrowding households are common in this area, as well as burn accidents due to the use of wood as the major fuel for cooking.

Molecular mechanism of sulphonylurea block of K(ATP) channels carrying mutations that impair ATP inhibition and cause neonatal diabetes.

Sulphonylurea drugs are the therapy of choice for treating neonatal diabetes (ND) caused by mutations in the ATP-sensitive K(+) channel (KATP channel). We investigated the interactions between MgATP, MgADP, and the sulphonylurea gliclazide with KATP channels expressed in Xenopus oocytes. In the absence of MgATP, gliclazide block was similar for wild-type channels and those carrying the Kir6.

Tetrameric structure of SUR2B revealed by electron microscopy of oriented single particles.

The ATP-sensitive potassium (K(ATP)) channel is a hetero-octameric complex that links cell metabolism to membrane electrical activity in many cells, thereby controlling physiological functions such as insulin release, muscle contraction and neuronal activity. It consists of four pore-forming Kir6.2 and four regulatory sulfonylurea receptor (SUR) subunits.