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Biomedical subjects

F Shimada

Publications and source records attributed to F Shimada.

At least 19 recordsLinked to original sources
PubMed2001

Analysis of the insulin-sensitive phosphodiesterase 3B gene in type 2 diabetes.

We screened for mutations in the gene of insulin-sensitive phosphodiesterase 3B (PDE3B), which regulates antilipolytic actions of insulin via reduction of intracellular cyclic AMP levels, in Japanese patients with type 2 diabetes mellitus and lipoatrophic diabetes mellitus using single-stranded conformation polymorphism analysis and Southern analysis and investigated frequencies of variable number of tandem repeats. A silent polymorphism at the Arg463 codon (AGG-->AGA) in exon 4 was identified after examining all 16 exons and exon-intron splicing junctions of the gene. This polymorphism was found in 53 of 100 subjects with type 2 diabetes mellitus, 2 of 5 lipoatrophic diabetic patients and 24 of 50 control subjects, without any significant difference in allele frequency between groups. An EcoRI restriction fragment length polymorphism was identified in patients with type 2 diabetes mellitus and control subjects, again with no differences in occurrence. The allelic distribution of two polymorphic tandem repeats sequences in introns 5 and 12 of the gene did not differ significantly between patients with type 2 diabetes mellitus and control subjects. In conclusion, alterations in the PDE3B gene are unlikely to contribute importantly to the pathogenesis of type 2 diabetes mellitus or lipoatrophic diabetes mellitus in Japan.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Angiotensin-converting enzyme inhibitors and probucol suppress the time-dependent increase in urinary Type IV collagen excretion of Type II diabetes mellitus patients with early diabetic nephropathy.

BACKGROUND: A multicenter prospective clinical trial was carried out in 9 National Hospitals in Japan to elucidate the time-dependent change in urinary Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or probucol is effective in preventing progression of renal involvement of diabetics by evaluating urinary Type IV collagen excretion. METHODS: Normo- and microalbuminuric patients with Type II DM were recruited. Patients were assigned to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV collagen excretion rate was also measured. RESULTS: Although, AER, urinary N-acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the control group did not vary over 24 months, urinary Type IV collagen excretion rate in the control group increased time-dependently (p < 0.01 vs baseline at 18 months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups, time-dependent increases in urinary Type IV collagen excretion rates were not observed. In the ACE-I group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 24 months (p < 0.05). In the probucol group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 6 months (p < 0.05). In the ACE-I group, AER decreased significantly compared with baseline at 18 months (p < 0.05) and at 24 months (p < 0.005). CONCLUSIONS: ACE-I has a beneficial effect and probucol may have a beneficial effect in preventing the progression of early diabetic nephropathy. Measurement of the urinary Type IV collagen excretion rate in combination with AER would be useful for the management of early renal involvement in Type II DM.

Acetylglucosaminidase↗
PubMed2000

Mutations in the hepatocyte nuclear factor-4alpha gene in Japanese with non-insulin-dependent diabetes: a nucleotide substitution in the polypyrimidine tract of intron 1b.

Mutations of the hepatocyte nuclear factor 4 alpha (HNF-4alpha) gene have been demonstrated in maturity-onset diabetes of the young (MODY) 1 families. To investigate the possibility that the HNF-4alpha gene contributes to the onset of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese patients, we screened all exons and flanking introns of this gene for mutations in 100 patients with NIDDM diagnosed after 25 years of age. We identified two missense mutations: M49V in exon 1c and T1301 in exon 4; and two nucleotide substitutions in introns: cytosine to thymidine at -5 nt in intron 1b and adenine to thymidine at -21 nt in intron 5. We screened an additional 220 diabetic subjects for the polymorphism in intron 1b. The c/t substitution in intron 1b was associated with NIDDM. This substitution in the polypyrimidine tract, an important cis-acting element directing intron removal, is likely to influence pre-mRNA splicing of this gene. T1301 in exon 4 was observed in only two diabetic subjects. This mutation could influence the conformation of this peptide, resulting in changes in ligand binding domain function. M49V in exon 1c was found in both diabetic and non-diabetic subjects; isoforms HNF-4alpha 4, 5, and 6 with this mutation may impair glucose metabolism in tissue. In contrast to the primary cause of nonsense and missense mutations of the HNF-4alpha gene in MODY1, the nucleotide substitution in intron 1b may partially contribute to development of NIDDM in combination with other genetic and environmental factors.

Aged↗
PubMed1999

The neuroprotective agent MS-153 stimulates glutamate uptake.

We investigated the effect of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a novel neuroprotective agent, on L-[3H]glutamate uptake through GLT-1, a Na(+)/K(+)-dependent glial glutamate transporter, expressed in COS-7 cells. MS-153 (1-100 microM) accelerated the L-[3H]glutamate uptake through GLT-1 in a concentration-dependent and time-dependent manner. Eadie-Hofstee analysis revealed that MS-153 significantly decreased the K(m) of the glutamate uptake by COS-7 cells expressing GLT-1. In contrast, [3H]gamma-aminobutyric acid (GABA) uptake through a glial GABA transporter was not affected. In addition, MS-153 increased Na(+) currents through GLT-1 expressed in Xenopus oocytes. We also investigated the effect of MS-153 on amino acid efflux from rat hippocampal slices. The increase in glutamate efflux induced by 50 mM KCl was significantly attenuated by the treatment with MS-153 at 10 microM, while MS-153 had no significant effect on the K(+)-evoked efflux of GABA. Furthermore, the increase in glutamate efflux by ischemia (hypoxia/aglycemia) was partially, but significantly inhibited by MS-153. These results suggest that the cerebroprotective effect of MS-153 in this ischemic model in vivo is due to the specific reduction of the glutamate concentration in the extracellular space, which can probably be attributed to the acceleration of glutamate uptake by the indirect modulation of the glutamate transporter activity.

ATP-Binding Cassette Transporters↗
PubMed1999

Differential diagnosis of cervical lymph nodes in head and neck cancer by ultrasonography.

OBJECTIVE: Determination of whether an enlarged cervical lymph node is metastatic or not is clinically important in head and neck oncology. Differential diagnosis of the lymph node, however, is still a diagnostic problem. The purpose of this study is to clarify the ultrasonographic findings of the metastatic lymph nodes of head and neck squamous cell carcinoma and to establish the criteria. METHODS: We investigated 36 metastatic lymph nodes in head and neck squamous cell carcinoma and 24 non-metastatic nodes in benign disease with a 10-MHz transducer. We examined the size, shape, and internal echo (echo level, punctate bright echogenic spots, hilus echogenic line, cystic pattern) of these nodes. Based on this investigation, we evaluated 70 lymph nodes from 25 other patients by ultrasonography. RESULTS: The short axis diameter and shape of metastatic nodes were larger and rounder than those of non-metastatic ones. Of the metastatic nodes, 69% showed hypoechoic and 31% isoechoic levels, and 78% exhibited punctate bright echogenic spots. Of the non-metastatic nodes, 92% showed hypoechoic and 8% isoechoic levels, and none of them showed the spots. The hilus echogenic line was not present in any metastatic node, but it was seen in 58% of non-metastatic ones. Of the metastatic nodes, 19% exhibited a cystic pattern; none of the non-metastatic nodes showed the pattern. According to our criteria based on these results, the accuracy rate was 98.6% (69/70). The sensitivity and specificity were 97.2% (35/36) and 100% (34/34), respectively. The false positive rate and the false negative rate were 0% (0/70) and 1.4% (1/70), respectively. CONCLUSION: Internal echo findings and shape of lymph nodes can be an important diagnostic tool, and our ultrasonographical criteria of the lymph nodes are very useful for the differential diagnosis of the cervical lymph nodes.

Biopsy↗
PubMed1998

A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro.

Cyclic adenosine 5'diphosphate-ribose (cADPR) is thought to have a second messenger role in insulin secretion through mobilisation of Ca2+. As human lymphocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activity, it may be important in glucose-induced insulin secretion in islets. Thirty one randomly selected Japanese patients with Type II diabetes mellitus who had first-degree and/or second-degree relative(s) with Type II diabetes mellitus were screened for mutations of this gene using single-stranded conformation polymorphism. Two variant patterns in exon 3 and exon 4 of the CD38 gene were identified. The variant in exon 3 resulted in an amino acid substitution from Arg140 (CGG) to Trp (TGG). The Arg140Trp mutation was observed in 4 of 31 patients, and allele frequencies were significantly different in patients and the control subjects (p = 0.004). One patient with this mutation has two missense mutations on beta cell/liver glucose transporter (GLUT2) gene; her mother, who has impaired glucose tolerance, also has this mutation on the CD38 gene and one missense mutation on the GLUT2 gene. Enzyme activity studies using COS-7 cells expressing the Arg140Trp mutation showed a reduction in ADP-ribosyl cyclase and cADPR hydrolase activity of around 50%. The Arg140Trp mutation on CD38 thus appears to contribute to the development of Type II diabetes mellitus via the impairment of glucose-induced insulin secretion in the presence of other genetic defects.

ADP-ribosyl Cyclase↗
PubMed1997

Thallium-201 single-photon emission tomography in the treatment follow-up of nasopharyngeal carcinoma.

In order to assess the usefulness of thallium-201 single-photon emission tomography (SPET) in the treatment follow-up of nasopharyngeal carcinoma (NPC), a total of 75 201T1 SPET studies were performed in 18 patients with histologically proven NPC. The findings were compared with those of magnetic resonance imaging (MRI) before and after therapy. Four patients received radiotherapy alone while the other 14 received concurrent chemo-radiotherapy. Treatment response was classified as complete (CR) or partial (PR) based on the findings of MRI and 201T1 SPET. Intense 201T1 uptake by the tumour was seen in all 18 patients before treatment. After treatment, MRI showed seven CRs and 11 PRs, whereas 201T1 SPET showed 13 CRs and five PRs. In 12 patients, the results of 201T1 SPET were in agreement with those of MRI. In six patients MRI showed PR but 201T1 showed CR. Follow-up (mean 10.6 months) MRI and 201T1 SPET studies of these six patients revealed that tumour gradually decreased and finally vanished in three patients. This preliminary study indicates that 201T1 SPET has potential in the assessment of early response to treatment of patients with NPC when compared with MRI.

Carcinoma↗
PubMed1997

Expression of human islet amyloid polypeptide/amylin impairs insulin secretion in mouse pancreatic beta cells.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated histopathologically with islet amyloid deposits of which a major component is islet amyloid polypeptide (IAPP)/amylin. We examined whether endogenous IAPP controls insulin secretion via a local effect within pancreatic islets and whether overexpression of this peptide contributes to pancreatic beta-cell dysfunction in this disease. Transgenic mice expressing human IAPP in pancreatic beta cell were used in this study. Human IAPP expression did not influence the mouse proinsulin mRNA level and insulin content. Glucose-induced insulin secretion was decreased in the isolated pancreatic islets of transgenic mice. MIN6, a glucose-responsive pancreatic beta-cell line, was transfected with human IAPP cDNA by a lipofectin method. Human IAPP expression was confirmed by RNA blot and immunohistochemical analysis. In two transfectants expressing the largest amount of human IAPP, insulin secretion was increased in response to glucose stimulation; however, the magnitude of the insulin response in cells transfected with human IAPP was smaller than in control clones. Insulin content was not influenced by the expression. We conclude that endogenous IAPP inhibits insulin secretion via an autocrine effect within pancreatic islets, and that the impaired insulin secretion in this disease may be partly caused by overexpression of IAPP.

Amyloid↗
PubMed1997

Cerebroprotective effects of a novel pyrazoline derivative, MS-153, on focal ischemia in rats.

MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline) is a novel pyrazoline compound that has potent cerebroprotective effects in the rat focal cerebral ischemia model. Middle cerebral artery (MCA) occlusion in rats allows detailed assessment of both functional and morphological sequelae of brain infarct. Using this model, we evaluated the cerebroprotective effects of MS-153. Treatment with MS-153 (12.5 mg/kg, i.v. bolus followed by 6.25 mg/kg/hr or 25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 7 days) significantly reduced infarct volumes and improved neurological deficits in MCA occluded rats 7 days after occlusion. Delayed treatment significantly reduced infarct volume 24 hr after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 21 hr) administration was started 3 hr after occlusion. Brain edema was also significantly improved when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 18 hr) administration was started 6 hr after occlusion.

Analysis of Variance↗
PubMed1997

[Ultrasonographic diagnosis of the parotid gland tumors--experience with 310 patients].

The diagnostic value of ultrasonography of parotid gland tumors is to determine if the tumor is benign or malignant. In the period from 1984 to 1995, ultrasound examinations were performed on 310 patients with a space-occupying lesion of the parotid gland, using real time 3.75 MHz, 5 MHz and 7.5 MHz transducers. From a histological standpoint, there were 246 benign tumors, namely 144 pleomorphic adenomas, 35 adenolymphomas, 23 other adenomas, 14 cysts, 9 neurinomas, 3 lymphomas, 9 hemangiomas, 3 lymphangiomas and 6 lymph nodes. Another 64 were malignant tumors, namely, 7 mucoepidermoid carcinomas, 7 acinic cell carcinomas, 7 adenoid cystic carcinomas, 15 adenocarcinomas, 7 squamous cell carcinomas, 4 undifferentiated carcinomas, 10 carcinomas in pleomorphic adenoma, 3 malignant lymphomas, 2 metastatic carcinomas and 2 other carcinomas. According to our criteria for ultrasonographic diagnosis of the parotid gland tumors, the benign or malignant pattern was determined by the following findings; shape, boundary echo, internal echo and posterior echo. But in some cases we could not differentiate the two echogram patterns, and we call them the intermediate pattern. The total accuracy rate of the diagnosis of the 310 patients was 79.0%. (The intermediated pattern was found in 39 patients and these cases were considered to be misinterpreted.) In 268 primary parotid gland tumors (210 benign and 58 malignant tumors) excluding recurrent cases, lymph nodes, hemangiomas and so on, the sensitivity was 62.1%, the specificity was 91.4% and the total accuracy rate was 85.1%. The accuracy of sonography in determining whether a tumor was benign or malignant was affected by the tumor size; tumors smaller than 2 cm in diameter showed a tendency to be diagnosed as benign and tumors larger than 6 cm in diameter as malignant. In the 268 cases, the importance of the pattern of the boundary echo and the internal echo in differentiating benign and malignant tumors was examined retrospectively. In the 210 primary benign tumors, the benignity of the tumors was assessed correctly in 84.3% by the boundary echo and 85.7% by the internal echo. In the 58 primary malignant tumors, the malignancy was assessed correctly in 58.6% by the boundary echo and 43.1% by the internal echo. Strong echos, which are the signs of a malignant pattern, were seen in 14.8% of the benign tumors, and in 51.7% of the malignant tumors. It can be concluded that ultrasonography is very reliable for the examination of parotid gland tumors.

Humans↗
PubMed1996

Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family.

Two distinct PDE3 [cyclic GMP-inhibited cyclic nucleotide phosphodiesterase (cGI PDE)] isoforms, cGIP1 and cGIP2, have been identified. Here we report cloning of the cDNA and gene encoding human (H)cGIP1 (classified as PDE3B). The cDNA encodes a protein of 1112 amino acids (approximately 123 kDa). Northern blots indicate that its mRNA is expressed in several adipose tissue depots. The human PDE3B gene is composed of 16 exons spanning more than 114 kb and was localized to chromosome 11p15 by in situ hybridization. Exon/intron boundaries were determined, and genetic polymorphism, confirmed by single-strand conformational polymorphism of DNA from 25 healthy subjects, was demonstrated in exon 4 at nucleotide 1389 (A/G). Two polymorphic dinucleotide repeat sequences were identified in introns 5 and 12.

Amino Acid Sequence↗
PubMed1996

Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subjects.

Hormone-sensitive lipase (HSL) plays an important role in energy metabolism by controlling the hydrolysis of triglycerides stored in adipose tissue. To investigate whether mutations in the HSL gene are associated with non-insulin-dependent diabetes mellitus (NIDDM), we screened for mutations of this gene using single-stranded conformation polymorphism (SSCP) in 35 Japanese subjects with NIDDM. SSCP analysis identified a variant pattern in axon 4, and the sequence showed that this variant pattern resulted from amino acid polymorphism (Arg309Cys). Subsequent study showed that this polymorphism was found in 18 of 151 NIDDM patients and 10 of 97 nondiabetic subjects, but allele frequency was not significantly different between the two groups (P = .7). Body mass index, serum triglyceride, and high-density lipoprotein (HDL) cholesterol were not different in subjects with and without the polymorphism. But serum total cholesterol was higher in subjects with the polymorphism than in subjects without it (P = .0005). These data indicate that this HSL polymorphism is not associated with NIDDM, obesity, and serum triglyceride level. However, an effect of the polymorphism to elevate serum total cholesterol has not been excluded, although further study is necessary to resolve its association with cholesterol metabolism.

Alleles↗
PubMed1995

Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2) glucose transporter in Japanese subjects.

The beta-cell/liver glucose transporter (GLUT2) gene was screened for mutations using single-strand conformation polymorphism analysis (SSCP) in 30 Japanese subjects with non-insulin dependent diabetes mellitus (NIDDM). Analysis of all exons and adjacent intron regions identified six SSCP polymorphisms, three of which resulted in amino acid substitutions: V101I, T110I and G519E. The V101I and G519E, substitutions represent new polymorphisms in this gene. The six polymorphisms were observed in both NIDDM and control groups and there were no significant differences in allele frequencies between groups. A portion of the insulin receptor substrate 1 gene in 30 NIDDM subjects and in normal control subjects was also screened for mutations. Two SSCP variants that change the sequence of the protein, delta S686/687 (deletion of the codons for serine-686 and 687) and G972R, were identified in two different NIDDM subjects, both whom were also heterozygous for the V101I polymorphisms in GLUT2. The GLUT2 and IRS1 amino acid polymorphisms did not show a simple pattern of co-inheritance with NIDDM in the families of these subjects suggesting that neither polymorphism is sufficient to cause NIDDM but may increase diabetes-susceptibility through their interaction with other loci and environmental factors.

Amino Acid Sequence↗
PubMed1995

A case of nodular fasciitis arising in the auricle.

Nudular fasciitis is an uncommon benign proliferative lesion in the head and neck, and is extremely rare in the auricle. A case of nodular fasciitis arising in the auricle of 53-year-old man is reported by immunohistochemical and electron microscopical studies. Initially, he had noticed a small painless nodule on the posterior side of right auricle, and it grew up rapidly in size over 2 months. A biopsy revealed nodular fasciitis. This lesion was resected totally with the auricular cartilage. Histological examination revealed proliferation of spindle-shaped cells and immunohistochemical-positive staining was observed with actin, and focally positive staining was seen with vimentin. Electron microscopically some tumor cells contained dilated rough endoplasmic reticulum and myofilament-like bundles in cytoplasm.

Actins↗
PubMed1995

Insulin resistance associated with decreased levels of insulin-receptor messenger ribonucleic acid: evidence of a de novo mutation in the maternal allele.

Mutations in the insulin receptor gene may lead to insulin resistance and diabetes mellitus in some patients. We have studied an insulin-resistant patient with leprechaunism. Insulin binding to the patient's fibroblasts was markedly decreased. Determination of the nucleotide sequence of the patient's insulin receptor gene revealed heterozygosity for a 2-basepair deletion in exon 15. If the premessenger ribonucleic acid (pre-mRNA) is spliced normally, it causes a replacement of codon 970 in the beta-subunit with a premature chain termination codon, thereby deleting most of the intracellular domain of the receptor. The mRNA transcribed from the allele with a 2-base-pair deletion is likely to be unstable because mRNA transcripts from this allele could not be detected by complementary DNA sequencing. Northern blot analysis showed that the patient's insulin receptor mRNA was decreased by 90% compared with that of a control subject, thus suggesting that the patient is a compound heterozygote for two mutations that decrease levels of insulin receptor mRNA. This deletion mutation in exon 15 seems to be a de novo mutation, because it was not detected in either parent. Investigation of the inheritance of a silent sequence polymorphism in exon 17 provided that the deletion occurred in the maternal allele. Furthermore, linkage analysis suggests that the second mutation is derived from the patient's father, although we could not directly identify it by sequencing the coding region of the insulin receptor gene. Therefore, it is possible that this mutation is present in a regulatory domain of the insulin receptor gene, acting in cis-dominant fashion to reduce the levels of insulin receptor mRNA. Analyses of the hypervariable region in the myoglobin and pMCT118 loci were consistent with the assumption that the father and mother studied here are indeed the biological parents of the diseased patient. We hereby conclude that the patient is a compound heterozygote for two mutant alleles, both of which are responsible for the reduced levels of insulin receptor mRNA and insulin binding.

Adult↗
PubMed1995

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin.

To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we developed transgenic mice using a human IAPP cDNA connected to an insulin promoter. Ribonucleic acid blotting and immunohistochemistry revealed the expression of the transgene in the pancreatic beta cells. Immunogold electron microscopy showed that beta-secretory granules contained the human C-terminal flanking peptide of the IAPP precursor. Reverse-phase HPLC demonstrated human and mouse IAPP amide in the pancreas. Electron microscopy showed the accumulation of fibril-like material in a considerable number of beta-secretory granules. These results suggest that in transgenic mice, the human IAPP precursor is expressed in beta cells and becomes normally sorted into beta-secretory granules in which normal conversion to mature human IAPP takes place. The human IAPP molecules, because of their amyloidogenesis, aggregate into amyloid fibrils in secretory granules. Glucose tolerance was normal at 7 months old and islet amyloid was not observed. A longer time may be required for islet amyloid deposits and hyperglycemia to develop in mice. Our working hypothesis is that in human NIDDM, IAPP aggregates into amyloid fibrils in beta-secretory granules, and that the fibrils are released into the extracellular space and islet amyloid deposits become substantial with time.

Amyloid↗
PubMed1994

Expression of the gene encoding the tyrosine kinase-deficient human insulin receptor in transgenic mice.

Defects in the insulin receptor (IR) in diabetic patients have been given much attention. To address the role of such defects, we generated a transgenic (TG) mouse carrying the cDNA encoding a tyrosine-kinase (TK)-deficient human IR (hIR), under the control of the native promoter. The TG mouse expressed the transgene (TG) mRNA in the liver, as identified in Northern blots. Analyses of various tissues by reverse transcription-polymerase chain reaction revealed that expressions of the TG mRNA in brain, heart, kidney, lung, stomach, skeletal muscle and adipose tissue were higher than those seen with the endogenous mouse IR (mIR), but expression in small intestine, colon, spleen, testis and ovary were approximately half those seen with the endogenous mIR. In the liver, the expression of the TG was about one tenth that of the endogenous mIR. In analyses of insulin binding and IR autophosphorylation, using a human-specific anti-IR antibody, the TK-deficient hIR was synthesized in the tissues of the TG mice. Despite the expression of TK-deficient hIRs in various tissues, including the major insulin-target tissues, muscle and adipose tissues, of the TG mice, no glucose intolerance was observed as assessed by the intraperitoneal glucose tolerance test, before and after sucrose feeding for 55 weeks. Our results suggest that a higher expression of the mutated IR, especially in the liver which is another major insulin-target tissue, or additional pathogenic factors, environmental or genetic, might be required for glucose intolerance.

Animals↗