Glucokinase

Glucokinase EC 2. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates, glucokinase. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, glucokinase shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or glucokinase fasting.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: 1 do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and 2 is glucokinase the alpha cell glucose sensor in this scenario.

Glucokinase

Federal government websites often end in. The site is secure. Glucose transport is by facilitated diffusion and is not rate limiting. Once inside, glucose is phosphorylated to glucosephosphate by GCK in a reaction that is dependent on glucose throughout the physiological range of concentrations, is irreversible, and not product inhibited. High glycerol phosphate shuttle, pyruvate dehydrogenase, and pyruvate carboxylase activities, combined with low pentose-P shunt, lactate dehydrogenase, plasma membrane monocarboxylate transport, and glycogen synthase activities constrain glucosephosphate to being metabolized through glycolysis. Under these conditions, glycolysis produces mostly pyruvate and little lactate. Pyruvate either enters the citric acid cycle through pyruvate dehydrogenase or is carboxylated by pyruvate carboxylase. Reducing equivalents from glycolysis enter oxidative phosphorylation through both the glycerol phosphate shuttle and citric acid cycle. Specific roles of different cell types are determined by the diverse molecular mechanisms used to couple energy state to cell specific responses. Having a common glucose sensor couples complementary regulatory mechanisms into a tightly regulated and stable glucose homeostatic network.

The role of GCK in liver is metabolic, i.

Official websites use. Share sensitive information only on official, secure websites. The GCK gene provides instructions for making a protein called glucokinase. This protein plays an important role in the breakdown of sugars particularly glucose in the body. Glucokinase is primarily found in the liver and in beta cells in the pancreas. Beta cells produce and release secrete the hormone insulin, which helps regulate blood glucose levels by controlling how much glucose is passed from the bloodstream into cells to be used as energy. Glucokinase acts as a sensor, recognizing when the level of glucose in the blood rises and helping stimulate the release of insulin from beta cells to control it.

Glucose metabolism in humans is tightly controlled by the activity of glucokinase GCK. GCK is predominantly produced in the pancreas, where it catalyzes the rate-limiting step of insulin secretion, and in the liver, where it participates in glycogen synthesis. A multitude of disease-causing mutations within the gck gene have been identified. Activating mutations manifest themselves in the clinic as congenital hyperinsulinism, while loss-of-function mutations produce several diabetic conditions. Indeed, pharmaceutical companies have shown great interest in developing GCK-associated treatments for diabetic patients. Due to its essential role in maintaining whole-body glucose homeostasis, GCK activity is extensively regulated at multiple levels. GCK possesses a unique ability to self-regulate its own activity via slow conformational dynamics, which allows for a cooperative response to glucose.

Glucokinase

Federal government websites often end in. The site is secure. Glucose metabolism in humans is tightly controlled by the activity of glucokinase GCK.

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The cells were incubated in either 4 mM glucose or 3 mM glucose sequentially without untreated or rising concentrations 0. Akt double KO mice lack hepatic GCK, are hyperglycemic, hypolipidemic, and moderately ketotic but have very high serum insulin levels. Rats were anesthetized with isoflurane Baxter, Kista, Sweden before decapitation. These results attest to importance of GCK activity on hepatic intermediary metabolism. The inhibitors were added to medium containing 4 mM glucose, each incubation lasted for 4 min, with a 4 min washout between inhibitor treatment and 3 mM glucose. Diabetes Obes. While beta cells respond to rising glucose levels by secreting insulin, alpha cells respond by reducing glucagon secretion. Alpha cells thus function as other glucose-sensing cells equipped with glucokinase. This promoter, in contrast to the liver promoter, has elements homologous to other insulin-induced gene promoters. The reaction catalyzed by glucokinase is:. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete.

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The common name, glucokinase, is derived from its relative specificity for glucose under physiologic conditions. References Agius L. Other transacting factors suspected of playing a role in liver cell transcription regulation include:. The two isoforms have the same kinetic and functional characteristics. The cells were transferred to sorting buffer HBSS containing 2. Possible mechanisms for how glucose metabolism by GCK and altered metabolite profiles could trigger insulin secretion were considered but possible mechanisms for stimulus secretion coupling were only speculative at this point Matschinsky et al. Received Oct 24; Accepted Feb 7. F6P decreases phosphorylation of glucose by GK when glycogenolysis or gluconeogenesis are underway. Although most of the glucokinase in the body is in the liver, smaller amounts in the beta and alpha cells of the pancreas, certain hypothalamic neurons, and specific cells enterocytes of the gut play an increasingly appreciated role in regulation of carbohydrate metabolism. Regulation of insulin release by calcium. Increased transcription can be detected in less than an hour after hepatocytes are exposed to rising insulin levels. Figure 1. Diabetes 39 , — Rats were anesthetized with isoflurane Baxter, Kista, Sweden before decapitation.