Metabolic diseases

Affecting the body’s homeostatic functions.

Accelerating metabolic disease research

Metabolic diseases, inborn errors of metabolism, include changes in cellular activity, and genetic mutations affecting proteins. As each organ has a specialized function, changes in gene expression, protein localization, and cell activity can affect glucose (pancreas), water, acid and salt (kidney), hormone levels (pituitary and adrenal glands), and protein and lipid homeostasis (liver). Also, gene mutations can alter protein function in mitochondria, affecting energy production and activity of muscle and brain cells, in organelles by disturbing lysosomal storage, and the liver. Some metabolic diseases can now be cured with gene therapies and enzyme replacement treatments.

Metabolic ion channels

and transporters

Varied targets
and mechanisms

Metabolic diseases are complex and varied and involve a wide range of mechanisms, genes, and proteins expressed in many cell types and organs in the periphery as well as the brain. Owing to their role in many basic cellular functions, ion channels and transporters are potential therapeutic targets for several metabolic diseases. In the case of endocrinological metabolic ailments, there are ion channels that regulate hormone release through modulation of membrane excitability (e.g. Nav and Kv channels), secretion (Ca2+ channels), and gene expression. A classic example is K-ATP (Kir6.x) channels which regulate pancreatic β cell insulin secretion and are the target of diabetes mellitus drugs such as tolbutamide, glibenclamide (glyburide), repaglinide, and nateglinide. As rare metabolic diseases include lysosomal storage disorders, the role of ion channels and transporters to regulate organelle ionic homeostasis, secretory and phagocytic function, and trafficking has revealed new targets for drug development. Transporters such as SGLT1 also regulate solute transport across many cell membranes, with the potential to ameliorate changes in sugars and nutrients in metabolic diseases.

Measuring SGLT1 on SURFE2R N1: EC50 for D-glucose transport

The figure shows the detection of Na+/sugar translocation using a sugar concentration jump in presence of sodium. Here we determined the KM for glucose transport by SGLT1. We performed a single solution exchange workflow by applying a D-glucose concentration jump in presence of 300 mM Na+. By application of different D-glucose concentrations in the range between 1 mM and 250 mM on the same sensor, we could determine the EC50 for D-glucose transport by SGLT1. We have used the same concentration of Mannitol as compensation in each substrate-free solution.

Assay platforms for

metabolic disease targets

Membrane transporters and channels

The SURFE2R N1 and  SURFE2R 96SE can measure ion and substrate flow by transporters and ion channels associated with metabolic disease. The activity of proteins inserted into bilayers or endogenously within native plasmalemma and organelle membranes can be biophysically and pharmacologically characterized to enable a better understanding of metabolic disease mechanisms and to screen for novel modulators.

A diverse set of transporters regulate the transfer of solutes, neurotransmitters, and counter-ions across cell membranes, with the potential to ameliorate pathophysiological changes in sugars and nutrients in metabolic disease. For example, the SGLT1 sodium-glucose co-transporter is responsible for the absorption of sugars from the gut and the reclamation of glucose from urine in the kidney. As ion channels and transporters regulate organelle ionic homeostasis, secretory and phagocytic function, and trafficking this makes them attractive drug targets to treat lysosomal storage and related metabolic diseases.

How can we help you?

Contact our specialist Dr. Cecilia George (HQ Senior Sales Manager SURFE2R / Senior Scientist ). Cecilia is delighted to help you:

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