KATP Assays
Background of KATP
KATP channel is a type of potassium ion channel that has a great affinity to changes in the concentration of intracellular ATP and ADP. KATP channel is very sensitive to the metabolic level of cells and couples ATP concentration to cell membrane potential in order to regulate a variety of physiological processes like excitatory contraction of blood vessels, heart, and skeletal muscles.
Fig.1. Structure Prediction of the Human Kir6.2. (Uniprot ID Q14654; obtained from Alphafold)
Distributions and Functions of KATP
KATP channel is initially described in cardiomyocytes, later in nerve cells, and skeletal muscle cells, recent researches also confirm its distribution in the vast majority of excitatory cells inside the human body. KATP channel links cellular metabolism and membrane excitability, thereby affecting the process of insulin excretion and glucose uptake.
Submembers and Mechanisms of KATP
KATP channel is a heterooctamer composed of two types of inwardly rectifying K+ channels and two types of ABC transporter sulfonylurea receptors.
| Channel | Gene | Mechanism | Activator | Blocker |
| Kir6.1 | KCNJ8 |
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| Kir6.2 | KCNJ11 |
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| SUR1 | ABCC8 |
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| SUR2 | ABCC9 |
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Assay List of KATP Channel
Creative Biolabs can provide a range of assays of KATP channels. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Genetic reduction of glucose metabolism preserves functional β-cell mass in KATP-induced neonatal diabetes |
| Journal | Diabetes |
| Published | 2022 |
| Abstract | The exhaustion and loss of β-cell function in the pancreas is a key event that marks the development and progression of multiple forms of diabetes. In pancreatic β-cells, KATP channels are responsible for glucose metabolism and insulin secretion, and KATP gain-of-function (GOF) mutations cause neonatal diabetes in humans. Exhaustion and loss of β-cell function in KATP-GOF mice and diabetes models suggest that different forms of diabetes may share common mechanisms independent of the underlying diabetic etiology. Glucose phosphorylation by glucokinase (GCK) is often the rate-limiting step in glucose metabolism and a regulator of insulin secretion. Sustained catalytic activation of β-cell GCK has been suggested as an underlying cause of the early compensatory increase in glucose sensitivity in type 2 diabetes, but overstimulation of β-cell metabolism has also been implicated as a culprit in subsequent Β-cell exhaustion and loss of β-cell mass. In this experiment, researchers hypothesized that chronic hyperglycemia increases β-cell blood-carrying activity, leading to glucotoxicity-induced β-cell exhaustion, which can be reversed by reducing β-cell glucose metabolism. In order to verify this hypothesis through in vivo experiments, β-cell-specific GCK haplotype-deficient mice and KATP-GOF-induced neonatal diabetic mice were constructed to detect the effect of GCK activity on the development of diabetes. |
| Result |
The experiment crossed mice carrying the β-cell-specific glucokinase haploinsufficiency gene with KATP-GOF mice to genetically reduce glucose metabolism to explore the protective effect of glucose on β-cell loss. The results showed that compared with KATP-GOF mice, KATP-GOF/GCK+/- mice had significantly lower blood glucose, delayed diabetes progression, normal body weight, restored adipose tissue function, and normalized metabolic efficiency. In contrast, plasma insulin content decreased, insulin glucagon increased, and proinsulin increased only in KATP-GOF mice. Strikingly, KATP-GOF/GCK+/- mice exhibited pronounced β-cell identity, whereas KATP-GOF mice showed increased β-cell dedifferentiation and significantly reduced identity. Overall, reducing β-cell glucose metabolism prevents glucose-induced loss of insulin content and β-cell failure, maintains adipose tissue, improves liver function, and metabolic parameters, and has also been shown to be independent between compensatory insulin hypersecretion and β-cell failure.
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Fig.2. Plasma hormones and cellular stress markers in two mouse models. (Yan, 2022)
Reference
- Yan, Z.; et al. Genetic reduction of glucose metabolism preserves functional β-cell mass in KATP-induced neonatal diabetes. Diabetes. 2022, 71: 1233-1245.
