Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus

Abstract

Impaired insulin-stimulated glycogen synthesis of skeletal muscle is among the most consistent pathophysiological characteristics of late-onset Type II diabetes and studies of glucose-tolerant first degree relatives of patients with late-onset Type II diabetes have shown that decreased insulin sensitivity in the whole body and impaired insulin-stimulated glycogen synthesis of skeletal muscle precede the onset of Type II diabetes [1]. The genetic basis of these findings, however, is mostly not known but genes encoding proteins, active in the continuously expanding network of interacting molecules constituting the insulin signalling pathways, are plausible candidates for insulin resistance and Type II diabetes [2]. Metabolic effects of insulin (glucose uptake and glycogen synthesis) Diabetologia (2001) Abstract Aim/hypothesis. Phosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By dephosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP 3 ) the PTEN protein regulates the insulin-dependent phosphoinositide 3-kinase (PI 3 K) signalling cassette and accordingly might function as a regulator of insulin sensitivity in skeletal muscle and adipose tissue. In this study we tested PTEN as a candidate gene for insulin resistance and late-onset Type II (non-insulin-dependent) diabetes mellitus in a Danish Caucasian population. Methods. The nine exons of the PTEN, including intronic flanking regions were analysed by PCR-SSCP and heteroduplex analysis in 62 patients with insulinresistant Type II diabetes. Corresponding author: Lars Hansen, MD, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Copenhagen, Denmark Abbreviations: PTEN, Phosphatase and tensin homlogue deleted from chromosome ten; PIP 3 , phosphatidyl-inositol-(3, 4, 5)-triphosphate; PI 3 K, phosphoinositide 3-Kinase; IVS, intronic variant sequence; PKB, protein kinase B; SSCP, single stranded conformation polymorphism; HOMA, homeostasis model of assessment.

Association of the polymorphisms in the 5′‐untranslated region of PTEN gene with type 2 diabetes in a Japanese population

“…Variants of the coding region in PTEN gene including SNP1–3 identified in the present study were not seen in Danish Caucasian patients with type 2 diabetes [23]. Conversely, four intronic polymorphisms identified in the Danish patients were not found in the current Japanese diabetic patients [23].…”

“…Variants of the coding region in PTEN gene including SNP1–3 identified in the present study were not seen in Danish Caucasian patients with type 2 diabetes [23]. Conversely, four intronic polymorphisms identified in the Danish patients were not found in the current Japanese diabetic patients [23]. Although it would be necessary to examine on a larger scale of Japanese subjects whether these intronic polymorphisms of PTEN gene are in fact not seen in Japanese populations, these differences may arise from a different genetic background between the two ethnic groups.…”

Impact of lipid phosphatases SHIP2 and PTEN on the time- and Akt-isoform-specific amelioration of TNF-α-induced insulin resistance in 3T3-L1 adipocytes

“…Taken together, inhibition of endogenous SHIP2 appears to be valuable in the amelioration of insulin resistance in type 2 diabetes. Concerning the pathological impact of PTEN in glucose homeostasis (10,13), heterozygous deletion of the PTEN gene in IRS-2 knockout mice conferred protection from insulin resistance, although homozygous disruption of the PTEN gene in mice resulted in embryonic lethality (19). Antisense oligonucleotide-mediated inhibition of endogenous PTEN expression in the liver led to the amelioration of elevated glucose levels and decreased insulin sensitivity in diabetic ob/ob and db/db mice (2).…”

PTEN mutations are common in sporadic microsatellite stable colorectal cancer

“…Marker positions and primer sequences were obtained from the Genome Database. Primers for the amplification of IVS4 þ 109 ins/del TCTTA and IVS8 þ 32 T/ G were as described by Zhou et al (2000) and Hansen et al (2001), respectively. After amplification, the IVS4 þ 109 ins/ del and IVS8 þ 32 T/G genotypes were determined by differential digestion of the respective PCR products with the restriction endonucleases AflII and HindII (Roche Molecular Biochemicals), respectively Zhou et al, 2000).…”