Novel target for diabetes drug identified as ion exchanger

We suggest endosomal Na/H exchangers (eNHE) as a potential target of metformin action. The eNHEs mostly exist in recycling endosomes and late endosomes to control the pH of these organelles. Metformin might affect the endosomal pathway by …more

Nagoya University-led researchers use nematode worms as a model to identify a new target of the type 2 diabetes drug metformin; ion exchanger protein NHX-5 and its related protein in fruit flies are potential metformin targets, suggesting the drug controls the cellular endocytic cycle.

This latest study found that metformin reduces L1 longevity, a survival response to starvation of the first larval stage, in C. elegans. A genetic screen identified a mutant worm resistant to metformin's action. The mutation was mapped to the endosomal sodium/hydrogen exchanger protein NHX-5, suggesting it could be used as a potential target.The most common type of diabetes, type 2, is characterized by insulin resistance and high blood glucose. Many patients are prescribed metformin, an anti-diabetic drug known to decrease hepatic glucose production and increase its uptake by muscle. Metformin also shows positive effects on other diseases such as polycystic ovary syndrome, nerve disorders, and some cancers. These versatile effects suggest that metformin could target multiple molecules, although details of its targets have remained unclear. A research team led by Nagoya University has now identified a novel potential target, a protein that mediates the exchange of sodium and hydrogen ions, using the model nematode Caenorhabditis elegans. The study was reported in the Journal of Biological Chemistry.

The fruit fly Drosophila is another model organism that researchers commonly use, and it was previously shown that metformin treatment reduces the lifespan of flies. In this study, the researchers tested mutant flies lacking NHE3, which is the homologous protein (one sharing an evolutionary history) to NHX-5 in Drosophila. They showed that NHE3 mutant flies are completely resistant to metformin. This result suggests that NHE is also the target of metformin in flies and that NHE may be a conserved target of metformin in other species.

NHX-5 is expressed in many parts of C. elegans, including the intestine and neurons. In the cell, it exists in the membranes of cellular components known as endosomes. Endosomes transport molecules such as proteins through a pathway that enables the sorted proteins to be secreted, recycled, or degraded. Treatment of C. elegans with metformin was shown to prevent formation of related cellular components known as autophagosomes, which are structures that break down cellular material, particularly during periods of starvation as a means of obtaining energy.

Metformin also reduced the oxygen consumption rate of C. elegans, hinting it may inhibit the function of mitochondria (cellular metabolic energy generators), as seen in mammals. "These findings suggest metformin targets NHX-5 to disrupt autophagy and related subcellular processes during L1 starvation in C. elegans, so that less energy is available," corresponding author Young-Jai You says. "This ultimately reduces L1 longevity, and supports a link between mitochondria and the endocytic cycle that is controlled by NHX-5."

Samsung offers financial incentives to stem Note 7 bleeding

Samsung on Thursday offered financial incentives for customers in South Korea who exchange Galaxy Note 7 smartphones for other Samsung models, as it scrambles to shore up its reputation in the wake of a damaging safety crisis.

Signage is seen at the Samsung 837 store in the Meatpacking District of Manhattan, New York, U.S., October 10, 2016. REUTERS/Andrew Kelly

The South Korean giant is in damage-control mode as rivals like Apple and LG try to steal market share from the global smartphone leader after it was forced to scrap its latest flagship device.

Samsung is boosting its marketing and promotional efforts around other Galaxy-series smartphones to cushion the blow from the demise of the premium Note 7, which it finally abandoned this week after failing to resolve overheating problems which caused some of the phones to ignite.

"Industry experience, such as the decline of Nokia and BlackBerry, shows how successful manufacturers can lose market share particularly quickly in the handset business," Fitch ratings agency said in a report.

In the United States, Samsung began sending fireproof boxes and protective gloves to customers returning potentially explosive Note 7s, drawing humorous barbs from social media commentators.

In its home market it started to offer refunds or exchanges for other products. Customers who returned their Note 7s, priced at about $880, were offered a coupon worth 30,000 won ($26.91), while those who chose an exchange for another high-end Samsung phone were promised an additional 70,000 won mobile credit.

The incentives would compensate consumers for their "big inconvenience," Samsung said in a statement.

On Wednesday the firm slashed its quarterly profit estimate by $2.3 billion to reflect the impact of the Note 7 withdrawal, giving some investors hope that the financial cost of the debacle had been largely accounted for.

"Samsung reflected most of the costs from the Note 7 in the Q3 earnings, reducing uncertainty about Q4 profit," analyst Jay Yoo at Korea Investment & Securities said.

But many analysts say the real risk to Samsung lies in the reputational damage it suffers in a cut-throat industry, which was harder to determine than financial costs.

"Potential long-term brand damage ... is a greater threat to its credit profile than the direct financial impact, which will be buffered by ample liquidity and a strong balance sheet," Fitch said.

Customers will have plenty of choice in the weeks ahead, with South Korean mobile carriers including SK Telecom planning to take pre-orders for Apple's iPhone 7 starting Friday. LG Electronics also recently launched its V20 smartphone.

Meanwhile South Korea's central bank said the Note 7 failure could undermine economic growth, although it needed more time to assess the effects.

5 ways how dieting makes us gain weight

A common mistake we make while dieting is over eating healthy food without keeping a track of the calories they got.Reuters

We have always believed that dieting can aid in shedding pounds, but it's not really true. Dieting can actually make you put on more weight. Here are some reasons why you tend to gain weight despite dieting hard:

Dieting makes you hog!

While we diet through the day expecting our weight to deplete, we end up eating lesser and starving more. This triggers hunger and our hunger hormones make us binge eat, i.e., we end up eating a lot. Hence, dieting makes us eat much more than we usually do and end up gaining more weight.

Irregular eating leads to weight gain

Dieting affects our metabolism rate. According to a study published by the American Journal of Clinical Nutrition, a group of women were asked to eat the usual amount of food they have at regular timings, or to eat erratically at unscheduled timings. The researchers observed that women eating at regular intervals burnt more calories than they did while eating unscheduled meals. The amount of insulin secreted by women when they had unplanned meal was comparatively less, which leads to weight gain.

Eating healthy foods in big proportions

Eating healthy foods is good for us, but we often forget that even healthy food have calories in them. Be it any nutritious food like fish, yogurt or baked chicken they all have calories in abundance and we should consume them in limited proportions when dieting and keep a track of the calorie intake.

Not dieting strictly

Most dieters have the habit of switching back to the old eating habits after achieving the short-term goals they made for losing weight loss. According to the estimation of the National Weight Control Registry, only 20 per cent of dieters lose weight successfully and they get back to eating the way they used to. It's also found that the dieters who strictly maintain their diet in the long run are likely to achieve and maintain their BMI 1.5 times more.

Consuming low-fat foods excessively

We often opt for low-fat food products while dieting and often end up eating them excessively, this makes us put on more weight. A research was conducted by the researchers of Cornell University in which they served candies labelled as "low-fat" or "regular". It was observed that people ate the candy with the low-fat label 28 per cent more. The researchers explained just because a product has low fats, it doesn't mean it's low on calories too.