Liver glycogen metabolism: An overview

Werve, Gérald van de; Jeanrenaud, B.

doi:10.1002/dmr.5610030104

Cited by 59 publications

(30 citation statements)

References 269 publications

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“…Increased hepatic glucose production results from the high availability of gluconeogenic precursors, such as amino acids (alanine and glutamine; as a result of accelerated proteolysis and decreased protein synthesis) (45), lactate (as a result of increased muscle glycogenolysis), and glycerol (as a result of increased lipolysis), and from the increased activity of gluconeogenic enzymes. These include PEPCK, fructose-1,6-biphosphatase, pyruvate carboxylase, and glucose-6-phosphatase, which are further stimulated by increased levels of stress hormones in DKA and HHS (46)(47)(48)(49)(50). From a quantitative standpoint, increased glucose production by the liver and kidney represents the major pathogenic disturbance responsible for hyperglycemia in these patients, and gluconeogenesis plays a greater metabolic role than glycogenolysis (46)(47)(48)(49)(50)51).…”

Section: Carbohydrate Metabolismmentioning

confidence: 99%

“…These include PEPCK, fructose-1,6-biphosphatase, pyruvate carboxylase, and glucose-6-phosphatase, which are further stimulated by increased levels of stress hormones in DKA and HHS (46)(47)(48)(49)(50). From a quantitative standpoint, increased glucose production by the liver and kidney represents the major pathogenic disturbance responsible for hyperglycemia in these patients, and gluconeogenesis plays a greater metabolic role than glycogenolysis (46)(47)(48)(49)(50)51). Although the detailed biochemical mechanisms for gluconeogenesis are well established, the molecular basis and the role of counterregulatory hormones in DKA are the subject of debate; very few studies have attempted to establish a temporal relationship between the increase in the level of counterregulatory hormones and the metabolic alterations in DKA (52).…”

Section: Carbohydrate Metabolismmentioning

confidence: 99%

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Management of Hyperglycemic Crises in Patients With Diabetes

et al. 2001

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Abbreviations: AaO 2 , alveolar-to-arteriolar oxygen; AKA, alcoholic ketoacidosis; ARDS, adult respiratory distress syndrome; BUN, blood urea nitrogen; CPT, carnitine palmitoyl-transferase; CSF, cerebrospinal fluid; DKA, diabetic ketoacidosis; FFA, free fatty acid; HHS, hyperosmolar hyperglycemic state; IRI, immunoreactive insulin; PaO 2 , arteriolar partial pressure of oxygen; RDKA, recurrent DKA.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Management of Hyperglycemic Crises in Patients With Diabetes T E C H N I C A L R E V I E R e v i e w s / C o m m e n t a r i e s / P o s i t i o n S t a t e m e n t s 132DIABETES CARE, VOLUME 24, NUMBER 1, JANUARY 2001Technical Review noted in newly diagnosed obese type 2 diabetic patients (5,26,31). Therefore, the concept that the presence of DKA in type 2 diabetes is a rare occurrence is incorrect.The most common types of infections are pneumonia and urinary tract infection, accounting for 30-50% of cases (Table 4). Other acute medical illnesses as precipitating causes include alcohol abuse, trauma, pulmonary embolism, and myocardial infarction, which can occur both in type 1 and 2 diabetes (6). Various drugs that alter carbohydrate metabolism, such as corticosteroids, pentamidine, sympathomimetic agents, and ␣-and ␤-adrenergic blockers, and excessive use of diuretics in the elderly may also precipitate the development of DKA and HHS.The recent increased use of continuous subcutaneous insulin infusion pumps that use small amounts of short-acting insulin has been associated with an incidence of DKA that is significantly increased over the incidence seen with conventional methods of multiple daily insulin injections, in spite of the fact that most of the mechanical problems with insulin pumps have been resolved (6,(32)(33)(34). In the Diabetes Control and Complications Trial, the incidence of DKA in patients on insulin pumps was about twofold higher than that in the multipleinjection group over a comparable time period (35). This may be due to the exclusive use of short-acting insulin in the pump, which if interrupted leaves no reservoir of insulin for blood glucose control.Psychological factors and poor compliance, leading to omission of insulin therapy, are important precipitating factors for recurrent ketoacidosis. In young female patients with type 1 diabetes, psychological problems complicated by eating disorders may be contributing factors in up to 20% of cases of recurrent ketoacidosis (36,37). Factors that may lead to insulin omission in younger patients include fear of weight gain with good metabolic control, fear of hypoglycemia, rebellion against authority, and stress related to chronic disease (36). Noncompliance with insulin therapy has been found to be the leading precipitating cause for DKA in urban African-Americans and medically indigent patients (5,26). In addition, a recent study showed that diabetic patients without health insurance or with Medicaid alone had hospitali...

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Section: Carbohydrate Metabolismmentioning

confidence: 99%

Section: Carbohydrate Metabolismmentioning

confidence: 99%

Management of Hyperglycemic Crises in Patients With Diabetes

et al. 2001

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“…Regulation of phosphorylase is incompletely understood. Phosphorylase has been postulated to be primarily regulated by the interconversion of the active, phosphorylated (phosphorylase a) and inactive, nonphosphorylated (phosphorylase b) forms (6,17,28,33,43,64). This important mechanism clearly plays a major role during stress, exercise, hypoxia, and hypoglycemia.…”

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confidence: 99%

Integrated effects of multiple modulators on human liver glycogen phosphorylasea

Ercan-Fang

Gannon

Rath

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Hepatic glucose production is increased in people with type 2 diabetes. Glucose released from storage in liver glycogen by phosphorylase accounts for ϳ50% of the glucose produced after an overnight fast. Therefore, understanding how glycogenolysis in the liver is regulated is of great importance. Toward this goal, we have determined the kinetic characteristics of recombinant human liver glycogen phosphorylase a (HLGPa) (active form) and compared them with those of the purified rat enzyme (RLGPa). The Michaelis-Menten constant (K m) of HLGPa for Pi, 5 mM, was about fivefold greater than the Km of RLGPa. Two Pi (substrate) concentrations were used (1 and 5 mM) to cover the physiological range for P i. Other effectors were added at estimated intracellular concentrations. When added individually, AMP stimulated, whereas ADP, ATP and glucose inhibited, activity. These results were similar to those of the RLGPa. However, glucose inhibition was about twofold more potent with the human enzyme. UDP-glucose, glucose 6-phosphate, and fructose 1-phosphate were only minor inhibitors of both enzymes. We reported previously that when all known effectors were present in combination at physiological concentrations, the net effect was no change in RLGPa activity. However, the same combination reduced HLGPa activity, and the inhibition was glucose dependent. We conclude that a combination of the known effectors of phosphorylase a activity, when present at estimated intracellular concentrations, is inhibitory. Of these effectors, only glucose changes greatly in vivo. Thus it may be the major regulator of HLGPa activity. glucose; glycogen metabolism; enzyme regulation; adenosine 5Ј-monophosphate; adenosine 5Ј-diphosphate; adenosine 5Ј-triphosphate; glucose 1-phosphate; fructose 1-phosphate; uridine 5Ј-diphosphate-glucose IN HUMANS, GLUCOSE RELEASED from liver glycogen by the enzyme phosphorylase accounts for ϳ50% of the total glucose produced after an overnight fast, significantly contributing to the maintenance of a normal blood glucose concentration (11,27,38,53,63). Despite increased serum glucose level in people with type 2 diabetes, phosphorylase-mediated glycogenolysis continues to contribute ϳ40-50% of overnight glucose production, inappropriately maintaining hyperglycemia (3,4,21,63, 68). Once glycogenolysis decreases, as with extended fasting, the blood glucose concentration decreases dramatically (3,20,24,32, 68). Therefore, understanding how phosphorylase-mediated glycogenolysis is regulated in people with or without diabetes is of considerable importance.Phosphorylase removes glycosyl units from the terminal branches of glycogen through phosphorolysis, forming glucose 1-phosphate. It is present in two interconvertible forms, phosphorylase a (phosphorylated) and b (unphosphorylated). The a form is the active form. Regulation of phosphorylase is incompletely understood. Phosphorylase has been postulated to be primarily regulated by the interconversion of the active, phosphorylated (phosphorylase a) and inactive, nonphospho...

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“…These hormonal changes increase glucose production from glycogenolysis and gluconeogenesis and impair glucose utilization by peripheral tissues, resulting in hyperglycemia, osmotic diuresis, electrolyte loss, dehydration, decreased glomerular filtration (further compounding hyperglycemia) and hyperosmolarity. [26,[30][31][32][33][34][35].…”

Section: Pathogenesismentioning

confidence: 99%

“…This is augmented by transient insulin resistance due to the hormone imbalance itself as well as the elevated free fatty acid concentrations [8,10,26,[28][29][30][31][32][33][34][35][36][37][38][39]. Uncontrolled hepatic fatty acid oxidation in the liver to ketone bodies (beta-hydroxybutyrate and acetoacetate) results ketonemia and metabolic acidosis [40].…”

Section: Pathogenesismentioning

confidence: 99%