Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and   cell failure

Porter, J. R.

doi:10.1136/jmg.2005.030791

Cited by 53 publications

(26 citation statements)

References 125 publications

(116 reference statements)

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“…Second, after glucose has entered the b-cell, it is phosphorylated to glucose-6-phospate by the high K M glucokinase (GK, hexokinase IV), which constitutes the flux determining step for glycolysis (Iynedjian 1993;De Vos et al 1995;Newgard & McGarry 1995;Matschinsky 1996) and is considered as the 'glucose sensor' in the pancreatic b-cell (Matschinsky 1996). The fact that mutations in the GK gene lead to impaired insulin secretion in maturity onset diabetes of the young type 2 patients further supports a role for GK as a glucose sensor (Porter & Barrett 2005). Third, once phosphorylated, glucose is metabolized by glycolysis to produce pyruvate, NADH and ATP.…”

Section: Proximal Glucose-sensing and Metabolic Signal Generation (A)mentioning

confidence: 97%

“…Deterioration of b-cell function also contributes to the progression of type 2 diabetes (Kahn 2000). As well, several monogenic forms of diabetes are directly linked to defects in the glucose-sensing machinery of the b-cell (Porter & Barrett 2005) and type 2 diabetes has been linked to polymorphisms in the glucose signal transduction machinery (Ashcroft & Rorsman 2004). Thus, knowledge of the mechanisms central to b-cell glucosesensing is critical toward understanding potential sites of dysfunction in type 2 diabetes, and potential targets for therapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

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Glucose-sensing mechanisms in pancreatic β-cells

MacDonald

Joseph

Rorsman

2005

Phil. Trans. R. Soc. B

297

265

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The appropriate secretion of insulin from pancreatic b-cells is critically important to the maintenance of energy homeostasis. The b-cells must sense and respond suitably to postprandial increases of blood glucose, and perturbation of glucose-sensing in these cells can lead to hypoglycaemia or hyperglycaemias and ultimately diabetes. Here, we review b-cell glucose-sensing with a particular focus on the regulation of cellular excitability and exocytosis. We examine in turn: (i) the generation of metabolic signalling molecules; (ii) the regulation of b-cell membrane potential; and (iii) insulin granule dynamics and exocytosis. We further discuss the role of well known and putative candidate metabolic signals as regulators of insulin secretion.

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Section: Proximal Glucose-sensing and Metabolic Signal Generation (A)mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Glucose-sensing mechanisms in pancreatic β-cells

MacDonald

Joseph

Rorsman

2005

Phil. Trans. R. Soc. B

297

265

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“…Diabetes mellitus is a chronic disorder of carbohydrate, fat and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin [16,34]. Diabetic individuals are at high risk of developing common metabolic complications which result in morbidity and mortality [39].…”

Section: Discussionmentioning

confidence: 99%

Hypoglycaemic Potentials of Frog oil in Alloxan-Induced Diabetic Rats

Okere¹

2014

AJBIO

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Abstract:The hypoglycaemic potentials of frog oil in alloxan-induced diabetic rats were investigated. Thirty six male albino rats weighing 120.47±2.52 g was completely randomized into six groups (A-F) comprising 6 animals each. Animals in group A (control) were administered 1 ml of distilled water while those in groups B, C, D, E and F were induced with diabetes mellitus by intraperitoneal administration of alloxan monohydrate (180mg/kg body weight) and in addition were respectively administered distilled water, metformin (a reference antidiabetic drug), 3, 6 and 9 mg/kg body weight of frog oil once daily. Treatment with the oil lasted for 14 days during which blood glucose level and selected biochemical parameters were determined. The results showed that there was significant (p<0.05) reduction in glucose levels in the group treated with 9.0 mg/kg body weight of the oil from 221.22±0.15 to 100.15±0.07 mg/dl, indicating the best antidiabetic activity of all the treatment groups. The oil also caused significant (p<0.05) decrease in serum total bilirubin levels from 8.73±0.07 µmol/L to 2.43±0.03 µmol/L; serum total cholesterol levels from 313.48±0.05 mmol/L to 232.40±0.19 mmol/L; liver aspartate aminotransferase (AST) activity from 76.93±0.02 U/L to 35.25±0.02 U/L; liver alanine aminotransferase (ALT) activity from 85.52±0.05 U/L to 39.71±0.08 U/L respectively. Overall, these findings established the fact that frog oil has hypoglycaemic potentials and thus can be recommended for use in the treatment of diabetes. The results from biochemical parameters indicated that frog oil could also be explored in the control of some of the metabolic dysfunctions normally associated with diabetes.

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“…Patients with type II diabetes mellitus (T2DM) are insulin resistant and glucose intolerant [Porter and Barrett, 2005], and epidemiological evidence supports the existence of a possible link between T2DM and AD. People with diabetes and insulin resistance have an increased risk of impaired cognition or dementia , and recent evidence from longitudinal studies suggests that diabetes increases risk of AD independent of vascular risk [Peila et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

Candidate gene association study of insulin signaling genes and Alzheimer's disease: Evidence for SOS2, PCK1, and PPARγ as susceptibility loci

Hamilton

Proitsi

Jehu

et al. 2007

American J of Med Genetics Pt B

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Epidemiological evidence supports the existence of a possible link between type II diabetes mellitus (T2DM) and late-onset Alzheimer's disease (LOAD). Polymorphisms from candidate genes for T2DM were genotyped in a two-stage approach to identify novel risk factors for LOAD. One hundred fifty-two polymorphisms were initially genotyped in a case:control cohort: nine SNPs showed individual association with disease status under at least one genetic model, while an additional two SNPs showed a haplotype association. In a replication study, we confirmed significant association of SNPs within three genes--PPARgamma, SOS2, and PCK1--with Alzheimer's disease. In particular, our data suggest that the effect of variants within these genes might be influenced by gender.

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Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and cell failure

Cited by 53 publications

References 125 publications

Glucose-sensing mechanisms in pancreatic β-cells

Glucose-sensing mechanisms in pancreatic β-cells

Hypoglycaemic Potentials of Frog oil in Alloxan-Induced Diabetic Rats

Candidate gene association study of insulin signaling genes and Alzheimer's disease: Evidence for SOS2, PCK1, and PPARγ as susceptibility loci

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