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1.
Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City Diabetes Study 总被引:7,自引:1,他引:7
Summary Although insulin resistance and decreased insulin secretion are characteristic of established non-insulin-dependent diabetes
mellitus (NIDDM), which of these metabolic abnormalities is the primary determinant of NIDDM is still controversial. A disproportionate
increase in the proinsulin to insulin ratio has been proposed as a marker of compromised insulin secretion. We examined the
association of fasting immunoreactive insulin (which cross-reacts with proinsulin), specific insulin (which does not cross-react
with proinsulin), total immunoreactive proinsulin (or insulin precursors), and the fasting proinsulin/specific insulin ratio
to the risk of developing NIDDM in the 3.25-year follow-up of the Mexico City Diabetes Study. These measurements were made
in 85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85 age and gender matched subjects who remained
non-diabetic at follow-up (control subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin ratio
were significantly higher in prediabetic than in control subjects. However, the relation between specific insulin and the
development of NIDDM was weaker than for proinsulin or immunoreactive insulin. After further adjustment for obesity, body
fat distribution and glucose tolerance status, proinsulin and the proinsulin/specific insulin ratio, but not specific or immunoreactive
insulin, predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted conversion to NIDDM both in subjects
with normal and those with impaired glucose tolerance at baseline. We conclude that in prediabetic subjects increased proinsulin,
a marker of islet cell distress or compromised insulin secretion, is associated with rapid conversion (within 3.25 years)
to NIDDM even in obese populations. [Diabetologia (1997) 40: 830–837]
Received: 29 November 1996 and in revised form: 12 March 1997 相似文献
2.
Quan Wen PhD Azazul Islam Chowdhury PhD Banu Aydin MD Mudhir Shekha PhD Rasmus Stenlid PhD Anders Forslund MD Peter Bergsten PhD 《Diabetes, obesity & metabolism》2023,25(12):3757-3765
Aim
To elucidate how proinsulin synthesis and insulin was affected by metformin under conditions of nutrient overstimulation.Materials and Methods
Isolated human pancreatic islets from seven donors were cultured at 5.5 mmol/L glucose and 0.5 mmol/L palmitate for 12, 24 or 72 h. Metformin (25 μmol/L) was introduced after initial 12 h with palmitate. Proinsulin and insulin were measured. Expression of prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE), was determined by western blot. Adolescents with obesity, treated with metformin and with normal glucose tolerance (n = 5), prediabetes (n = 14), or type 2 diabetes (T2DM; n = 7) were included. Fasting proinsulin, insulin, glucose, 2-h glucose and glycated haemoglobin were measured. Proinsulin/insulin ratio (PI/I) was calculated.Results
In human islets, palmitate treatment for 12 and 24 h increased proinsulin and insulin proportionally. After 72 h, proinsulin but not insulin continued to increase which was coupled with reduced expression of PC1/3 and CPE. Metformin normalized expression of PC1/3 and CPE, and proinsulin and insulin secretion. In adolescents with obesity, before treatment, fasting proinsulin and insulin concentrations were higher in subjects with T2DM than with normal glucose tolerance. PI/I was reduced after metformin treatment in subjects with T2DM as well as in subjects with prediabetes, coupled with reduced 2-h glucose and glycated haemoglobin.Conclusions
Metformin normalized proinsulin and insulin secretion after prolonged nutrient-overstimulation, coupled with normalization of the converting enzymes, in isolated islets. In adolescents with obesity, metformin treatment was associated with improved PI/I, which was coupled with improved glycaemic control. 相似文献3.
G. Velho H. Blanché M. Vaxillaire C. Bellanné-Chantelot V. C. Pardini J. Timsit P. Passa I. Deschamps J.-J. Robert I. T. Weber D. Marotta S. J. Pilkis G. M. Lipkind G. I. Bell P. Froguel 《Diabetologia》1997,40(2):217-224
Summary Mutations in glucokinase are associated with defects in insulin secretion and hepatic glycogen synthesis resulting in mild
chronic hyperglycaemia, impaired glucose tolerance or diabetes mellitus. We screened members of 35 families with features
of maturity-onset diabetes of the young for mutations in the glucokinase gene and found 16 different mutations. They included
14 new mutations in the glucokinase gene: 9 missense mutations (A53S, G80A, H137R, T168P, M210T, C213R, V226M, S336L and V367M);
2 nonsense mutations (E248X and S360X); a deletion of one nucleotide resulting in a frameshift (V401del1); a substitution
of a conserved nucleotide at a splice acceptor site (L122-1G → T); and a 10 base pair deletion that removed the GT of the
splice donor site and the following eight nucleotides (K161 + 2del10). In addition, we found two previously identified mutations:
R186X and G261R. Study of 260 subjects with glucokinase-deficient hyperglycaemia from 42 families with 36 different GCK mutations made it possible to define the clinical profile of this subtype of non-insulin-dependent diabetes mellitus (NIDDM).
Hyperglycaemia due to glucokinase deficiency is often mild (fewer than 50 % of subjects have overt diabetes) and is evident
during the early years of life. Despite the long duration of hyperglycaemia, glucokinase-deficient subjects have a low prevalence
of micro- and macro-vascular complications of diabetes. Obesity, arterial hypertension and dyslipidaemia are also uncommon
in this form of NIDDM. [Diabetologia (1997) 40: 217–224]
Received: 9 July 1996 and in revised form: 16 October 1996 相似文献
4.
5.
Oda N Nakai A Fujiwara K Imamura S Fujita T Hamagishi M Kato T Kobayashi T Himeno Y Yamamoto K Makino M Kakizawa H Sawai Y Itoh M Nagasaka A 《Metabolism: clinical and experimental》2001,50(6):631-634
We have sequenced the insulin gene in 72 unrelated Japanese subjects (52 with type 2 diabetes mellitus and 20 with normal glucose tolerance). We identified 6 mutations and all were found at a low frequency (1% to 4%). Three mutations were new. These included a C-to-G substitution in the promoter region, a G-to-A substitution in codon-2 resulting in an Ala-to-Thr replacement in amino acid -2 of the signal peptide, and a G-to-A substitution in intron 2. We have no evidence that any of the mutations that we found are the cause of diabetes. Thus, mutations in the insulin gene do not appear to be an important genetic factor contributing to the development of diabetes in this population. 相似文献
6.
Summary We investigated the possible association between alleles of a simple tandem repeat DNA polymorphism in the human glycogen
synthase gene and non-obese non-insulin-dependent diabetes (NIDDM) in Japanese subjects. Nine alleles (−4G, −3G, −2G, −1G,
0G, 1G, 2G, 3G, and 4G) were identified in the study group of 164 patients with NIDDM and 115 non-diabetic subjects. The overall
frequency distribution of the glycogen synthase gene alleles was significantly different between the two groups (p =0.0316). The 2G allele was found more frequently in patients with NIDDM than in non-diabetic subjects (17.7 % vs 8.7 %,
p =0.0016). These results suggest that the 2G allele could be a genetic marker of NIDDM in Japanese subjects. [Diabetologia
(1994) 37: 536–539]
Received: 13 November 1993 and in revised form: 3 January 1994 相似文献
7.
Role of type IV collagen in prolactin release from anterior pituitaries of male rats 总被引:1,自引:0,他引:1
We previously demonstrated that laminin, a component of basement membranes, modulates pituitary hormone secretion. In the
present study, we evaluated the effect of type IV collagen, another component of this membrane, on the release of prolactin
(PRL) by anterior pituitary gland from adult male rats. Hemipituitaries were incubated for 3 h with type IV collagen or antibodies
against it and PRL release was studied. Rabbit IgG to type IV collagen at concentrations of 10−7−10−5
M had a significant stimulatory effect on PRL release, in comparison to normal rabbit serum IgG or medium alone used as controls.
Type IV collagen induced a significant inhibitory effect on basal release of PRL at a concentration of 30 μg/mL. A slight
decrease in PRL release was detected in thyrotropin-releasing hormone-stimulated hemipituitaries incubated with type IV collagen
at all concentrations used. These results suggest that type IV collagen, similar to laminin-1, modulates PRL released from
hemipituitaries, in vitro. 相似文献
8.
S. A. Urhammer L. T. Dalgaard T. I. A. Sørensen A. M. Møller T. Andersen A. Tybjærg-Hansen T. Hansen J. O. Clausen H. Vestergaard O. Pedersen 《Diabetologia》1997,40(10):1227-1230
Summary Recently, a gene encoding a novel human uncoupling protein, designated UCP2, was discovered. The murine UCP2 was mapped to
a region on mouse chromosome 7 which in several models has been shown to be linked to obesity and hyperinsulinaemia. Single
strand conformation polymorphism (SSCP) analysis and direct sequencing of the coding region of the UCP2 gene in 35 obese Caucasian
NIDDM patients of Danish ancestry revealed one nucleotide substitution, replacing an alanine with a valine at codon 55. The
amino acid polymorphism was present in 24 of the 35 (69 %) examined subjects. The allelic frequency of the A/V55 variant was
48.3 % (95 % CI: 42.5–54.1 %) among 144 subjects with juvenile onset obesity, 45.6 % (40.5–50.7 %) among 182 subjects randomly
selected at the draft board examination, and 45.5 % (37.1–53.9 %) among lean control subjects selected from the same study
cohort. Within these cohorts there were no differences in BMI values at different ages among wild-type carriers and A/V55
carriers. In a population-based sample of 369 young healthy Caucasians the variant showed no association with alterations
in BMI, waist-to-hip ratio, fat mass or weight gain during childhood or adolescence. The A/V55 polymorphism was not related
to alterations in fasting values of serum insulin and C-peptide or to an impaired insulin sensitivity index. We conclude that
genetic variability in the human UCP2 gene is not a common factor contributing to NIDDM in obese Danish Caucasian subjects
and the common A/V55 amino acid polymorphism of the gene is not implicated in the pathogenesis of juvenile or maturity onset
obesity or insulin resistance in Caucasians. [Diabetologia (1997) 40: 1227–1230]
Received: 20 June 1997 相似文献
9.
M. P. Bulman M. J. Dronsfield T. Frayling M. Appleton S. C. Bain S. Ellard A. T. Hattersley 《Diabetologia》1997,40(7):859-862
Summary Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes mellitus (NIDDM) characterised
by an early age of onset (< 25 years) and an autosomal dominant mode of inheritance. MODY is genetically heterogeneous with
three different genes identified to date; hepatocyte nuclear factor 4 alpha (HNF-4α) [MODY1], glucokinase [MODY2] and hepatocyte
nuclear factor 1 alpha (HNF-1α) [MODY3]. A nonsense mutation in the HNF-4α gene has recently been shown to cause MODY in a
single large North American pedigree (RW). We screened a large UK Caucasian MODY family which showed weak evidence of linkage
to the MODY1 locus on chromosome 20q (lod score for ADA 0.68 at θ = 0) for mutations in the coding region of the HNF-4α gene by direct sequencing. A missense mutation resulting in the substitution
of glutamine for glutamic acid was identified in exon 7 (E276Q). The mutation was present in all of the diabetic members of
the pedigree plus two unaffected subjects and was not detected in 75 normal control subjects or 95 UK Caucasian subjects with
late-onset NIDDM. This is the first missense mutation to be described in the HNF-4α gene. [Diabetologia (1997) 40: 859–862]
Received: 7 March 1997 and in revised form: 16 April 1997 相似文献
10.
Summary Disruption of the melanocortin-4 (MC-4) receptor gene in mice results in maturity-onset obesity, hyperinsulinaemia and hyperglycaemia.
These phenotypes are characteristic of human obesity that frequently accompanies non-insulin-dependent diabetes. It is therefore
possible that human MC-4 receptor gene mutations contribute to human obesity. To test this possibility, we examined by DNA
sequencing the entire coding region of the human MC-4 receptor gene in 40 morbidly obese (BMI > 35 kg/m2) white British males and examined the 5′- and 3′-flanking regions in 20 out of these obese subjects. We also sequenced all
these regions in 10 lean (BMI < 18 kg/m2) white British males for a reference. We identified a single nucleotide substitution that replaces valine with isoleucine
at codon 103, in two obese subjects in the heterozygous state. No other nucleotide alterations were found. The prevalence
of this missense variant was studied in 322 white British males (190 with BMI > 28 kg/m2 and 132 with BMI < 22 kg/m2) selected from a population-based epidemiological survey. In these subjects, no homozygotes for the isoleucine allele were
found. The frequency of heterozygotes was similar (4.2 vs 4.5 %) in the two groups and there was no significant difference
in BMI, total skinfold thickness, plasma insulin and glucose levels between heterozygotes and codon-103 valine homozygotes
in either group. These results suggest that coding sequence mutations in the MC-4 receptor gene are unlikely to be a major
cause of human obesity, at least in white British males. [Diabetologia (1997) 40: 976–979]
Received: 10 March 1997 and in revised form 9 May 1997 相似文献
11.
A. M. Møller S. A. Urhammer L. T. Dalgaard R. Reneland L. Berglund T. Hansen J. O. Clausen H. Lithell O. Pedersen 《Diabetologia》1997,40(8):980-983
Summary Mutations in the hepatocyte nuclear factor-4α (HNF-4α) gene cause the type 1 form of maturity onset diabetes of the young
(MODY1). To address the question of whether genetic variability of HNF-4α is associated with late onset non-insulin-dependent
diabetes mellitus (NIDDM) we have sequenced the coding region and intron/exon boundaries of the gene in 36 randomly recruited
Danish NIDDM patients. Two nucleotide substitutions that changed the sequence of HNF-4α were identified: Thr/Ile130, which
has been reported previously and a novel Val/Met255. The Val/Met 255 mutation was found in 4 of 477 Danish NIDDM patients
and in none of 217 glucose tolerant control subjects; thus it cannot be excluded that this mutation may have an impact on
NIDDM susceptibility. Among 509 NIDDM patients the allelic frequency of the Thr/Ile130 variant was 4.7 % (95 % confidence
interval: 3.4–6.0 %) compared to 1.9 % (0.7–3.1 %) among 239 control subjects (p = 0.008). However, in a population sample of 942 Swedish men with an average age of 70 years the allelic frequency of the
variant was similar in 246 men with either impaired glucose tolerance (5.6 % [2.6–8.6 %]) or NIDDM (5.4 % [2.7–8.1 %]) as
compared to 666 glucose tolerant men (5.1 % [3.9–6.3 %]). Also in a population sample of 369 young healthy Danes the prevalence
of the codon 130 variant (4.7 % [3.2–6.2 %]) was similar to what was found in Swedish Caucasians. Thus, the allelic frequency
of the Thr/Ile130 variant among the control subjects in the Danish case-control study deviates from the prevalence in the
two other studies which is why we consider the significant association between the codon 130 variant and NIDDM an incidental
finding. In glucose tolerant subjects the codon 130 variant in its heterozygous form had no major effect on glucose-induced
insulin and C-peptide release although a tendency to a lower insulin secretion during an oral glucose tolerance test was seen
in middle-aged subjects. In conclusion, variability in the coding region of the HNF-4α gene is not a common cause of NIDDM
among whites of Danish ancestry. However, a Val/Met255 mutation was found exclusively in NIDDM patients (0.8 % of cases) and
functional as well as family segregation studies are needed to determine whether this HNF-4α variant is a NIDDM causing mutation.
[Diabetologia (1997) 40: 980–983]
Received: 17 April 1997 and in revised form: 28 May 1997 相似文献
12.
Summary Mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is thought to be an important factor for glucose sensing
in pancreatic beta cells. To evaluate the significance of the mGPDH gene in the development of non-insulin-dependent diabetes
mellitus (NIDDM), we set up primers and conditions for polymerase chain reaction (PCR) amplification of the coding exons and
flanking regions. Screening of 100 Japanese NIDDM patients for mutations using the PCR-single strand conformation polymorphism
(SSCP) method revealed four variants (ACA:Thr243-ACG:Thr243, CAT:His264-CGT:Arg264, GCA:Ala305-GCC:Ala305, GCA:Ala 306-TCA:Ser306).
The His264-Arg264 variant was found in 36 patients, while the other variants were found in only one patient each. Neither
the genotypic (χ2 = 3.15, p = 0.21) nor the allelic (χ2 = 2.27, p = 0.13) frequency of the His264-Arg264 mutation differed between 253 Japanese NIDDM patients and 157 non-diabetic subjects.
In addition, in NIDDM patients, neither the treatment modality nor body mass index differed between those with and without
this mutation. These results suggest that inherited defects at this locus do not make a major contribution to genetic susceptibility
to NIDDM in the Japanese population. [Diabetologia (1997) 40: 339–343]
Received: 14 August 1996 and in revised form: 5 December 1996 相似文献
13.
Y. Zhang N. Wat I. M. Stratton M. G. Warren-Perry M. Orho L. Groop R. C. Turner 《Diabetologia》1996,39(12):1505-1511
Summary Insulin receptor substrate-1 (IRS-1), β3-adrenergic-receptor (β3-AR) and glycogen synthase (GS) genes are candidate genes
for non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, dyslipidaemia and obesity. We studied white Caucasian
subjects with NIDDM, 227 being randomly selected, 49 NIDDM within the top two percentiles of insulin resistance; 54 with dyslipidaemia
in the top quintile of triglyceride/insulin and the bottom quintile of HDL, and 166 non-diabetic control subjects. We examined
the association of the simple tandem repeat DNA polymorphisms (STRPs) near the IRS-1 and GS genes, and the prevalence of mutations
at codons of IRS-1 513 and 972, β3-AR 64 and GS 464 using restriction fragment length polymorphism (RFLP). The STRP alleles
in IRS-1 were significantly different between NIDDM and control subjects (p = 0.015). The IRS-1 972 mutation was significantly different between the four groups with increased prevalence in the insulin
resistant and dyslipidaemia subjects (18 and 26 % compared with 11 % in control subjects; p < 0.0005). Those with or without IRS-1 mutations had similar clinical characteristics and impaired insulin sensitivity. β3-AR
64 mutation was not significantly different between the four groups but those with the mutation were more obese, with a test
for linear association between number of alleles and degree of obesity in an analysis of variance showing a significant association
(p = 0.029). The GS 464 mutation was not detected in any of the diabetic or control subjects and the population association
study using GS STRP showed no difference in allelic frequencies between NIDDM patients and control subjects. A mutation in
lipoprotein lipase at codon 291, associated in the general population with low HDL cholesterol, was not at increased prevalence
in the NIDDM patients with dyslipidaemia. In conclusion, IRS-1 972 had an increased prevalence in subjects with insulin resistance,
with or without dyslipidaemia. β3-AR 64 was associated with increased obesity but not with insulin resistance or dyslipidaemia.
These separate contributions to different features of NIDDM are an example of the polygenic inheritance of this heterogeneous
disorder. [Diabetologia (1996) 39: 1505–1511]
Received: 9 April 1996 and in revised form: 5 August 1996 相似文献
14.
S.-L. Wang W.-H. Pan C.-M. Hwu L.-T. Ho C.-H. Lo S.-L. Lin Y.-S. Jong 《Diabetologia》1997,40(12):1431-1438
Summary Our aim is to determine non-insulin-dependent diabetes mellitus (NIDDM) incidence in Taiwan and examine its relation to obesity
and hyperinsulinaemia in Chinese men and women. A total of 995 men and 1195 women aged 35–74 years free from diabetes in two
townships in Taiwan were followed up with a second examination. At baseline general and metabolic data were recorded, and
detailed anthropometric parameters and plasma glucose and insulin were assessed. World Health Organisation (WHO) criteria
of fasting glucose 7.8 mmol/l or greater was utilized for defining diabetes. The age-standardized incidence rate based on
the United States population in 1970 was 9.3/1000 (CI 5.8–12.8) in men and 9.3/1000 (CI 6.2–12.4) in women and the based on
the WHO population in 1976 was 8.9/1000 (CI .5–12.3) in men and 8.9/1000 (CI 5.9–11.9) in women for the Chinese who had a
mean BMI slightly greater than 24 (kg/m2). The predictability of the plasma glucose level was greater than that of the insulin level and the obesity indices. NIDDM
incidence increased approximately threefold with each 0.67 mmol/l increase in plasma glucose level in men and women. The present
study demonstrated the essential relationship of not only BMI but also central obesity indices (such as subscapular and waist
circumference) to the incidence of NIDDM among men and women and a stronger relationship between NIDDM incidence and obesity
in women than in men. The predictive effects of obesity indices and fasting plasma insulin values on NIDDM risk were independent
of each other in men. Obesity and hyperinsulinaemia each without the presence of the other can lead to an increased risk of
NIDDM. In women the NIDDM incidence increased more than additively in those with both obesity and hyperinsulinaemia compared
to those with single obesity or hyperinsulinaemia. A slightly higher incidence of NIDDM in Taiwan than in western countries
was found. The importance of obesity is indicated for predicting NIDDM in the community. Hyperinsulinaemia was found to play
a significant role in predicting NIDDM incidence independent of obesity in men and synergistically with obesity in women.
[Diabetologia (1997) 40: 1431–1438]
Received: 20 January 1997 and in final revised form: 11 June 1997 相似文献
15.
T Shiinoki T Suehiro Y Ikeda M Inoue T Nakamura Y Kumon Y Nakauchi K Hashimoto 《Metabolism: clinical and experimental》1999,48(5):581-584
We examined genetic mutations in the coding regions of the uncoupling protein 2 (UCP2) gene in 100 patients with non-insulin-dependent diabetes mellitus (NIDDM). The sequences of each exon-intron boundary were detected by polymerase chain reaction (PCR) using specific primer pairs designed in the cDNA sequence of UCP2 and a cycle-sequence method. Using the specific primer pairs in the intron 5'- or 3'-untranslated region, each exon with its exon-intron boundaries was amplified with the PCR method, and the PCR products were analyzed using a single-strand conformation polymorphism (SSCP) method. One nucleotide substitution in exon 4 was found, which exchanged Ala (gcc) at position 55 of the amino acid sequence for Val (gtc), previously reported in Denmark by Urhammer et al in 1997. The polymorphism was reanalyzed in all patients and 120 normal subjects using a PCR-restriction fragment length polymorphism method. There was no difference in the genotype distribution between patients and normal subjects, and our genotype distribution was similar to the Danish study. Furthermore, there were no clinical differences between genotype groups among the patients. No other mutation including the exon-intron boundary was found in these patients. Genetic mutations of UCP2 may not be commonly associated with obesity or diabetes in Japanese subjects. 相似文献
16.
Vivian Hook Lydiane Funkelstein Thomas Toneff Charles Mosier Shin-Rong Hwang 《Endocrine》2009,35(3):429-437
The production of the peptide hormones ACTH, α-MSH, and β-endorphin requires proteolytic processing of POMC which is hypothesized
to utilize dual cysteine- and subtilisin-like protease pathways, consisting of the secretory vesicle cathepsin L pathway and
the well-known subtilisin-like prohormone convertase (PC) pathway. To gain knowledge of these protease components in human
pituitary where POMC-derived peptide hormones are produced, this study investigated the presence of these protease pathway
components in human pituitary. With respect to the cathepsin L pathway, human pituitary contained cathepsin L of 27–29 kDa
and aminopeptidase B of ~64 kDa, similar to those in secretory vesicles of related neuroendocrine tissues. The serpin inhibitor
endopin 2, a selective inhibitor of cathepsin L, was also present. With respect to the PC pathway, human pituitary expresses
PC1/3 and PC2 of ~60–65 kDa, which represent active PC1/3 and PC2; peptide hormone production then utilizes carboxypeptidase
E (CPE) which is present as a protein of ~55 kDa. Analyses of POMC products in human pituitary showed that they resemble those
in mouse pituitary which utilizes cathepsin L and PC2 for POMC processing. These findings suggest that human pituitary may
utilize the cathepsin L and prohormone convertase pathways for producing POMC-derived peptide hormones. 相似文献
17.
P. M. Clark Dr. J. C. Levy L. Cox M. Burnett R. C. Turner C. N. Hales 《Diabetologia》1992,35(5):469-474
Summary Plasma insulin, intact proinsulin and 32–33 split proinsulin measured by specific immunoradiometric assays and insulin and
C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects
with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 ± 1.0
mmol/l (mean ± SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay
were 33 higher than insulin and 16 % higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic
and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32–33 split proinsulin. The
ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0 % (6.8–21.0
%, 1 SD range) and 6.3 % (4.0–9.8 %), respectively,p < 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non-diabetic subjects had similar
intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin
secretion by immunoradiometric assay (geometric means 55 and 101 pmol/1,p < 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/1,p < 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/1,p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were
subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination ( subnormal
responses in six of ten and eight of ten, respectively). Thus, raised proinsulin and proinsulin:total insulin ratio are not
necessarily a feature of mild diet-treated Type 2 diabetic patients with subnormal insulin responses to glucose. 相似文献
18.
Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects 总被引:12,自引:0,他引:12
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Nishigori H Tomura H Tonooka N Kanamori M Yamada S Sho K Inoue I Kikuchi N Onigata K Kojima I Kohama T Yamagata K Yang Q Matsuzawa Y Miki T Seino S Kim MY Choi HS Lee YK Moore DD Takeda J 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(2):575-580
19.
The beta cell glucokinase promoter variant is an unlikely risk factor for diabetes mellitus 总被引:1,自引:0,他引:1
K. Lotfi G. Sund R. Lowe J. Graham M. Landin-Olsson I. Kockum S. Deeb Å. Lernmark 《Diabetologia》1997,40(8):959-962
Summary Glucokinase plays an important role in the regulation of insulin secretion and is therefore an attractive candidate gene
for both insulin dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. A single G-A nucleotide polymorphism
at the –30 position of the beta-cell specific promoter region of the glucokinase gene was previously associated with reduced
beta-cell function. In the present study we analysed 268 consecutive newly diagnosed Swedish patients classified with either
IDDM (n = 205), NIDDM (n = 31) or unclassifiable (n = 32) diabetes between the ages of 15 and 35 years along with a group of 158 age- and sex-matched control subjects. The beta-cell
promoter region was amplified by the polymerase chain reaction and the G-A variant identified by single strand conformational
polymorphism. There was no significant difference in allele frequencies of G and A between any of the subject groups and likewise,
no significant difference in the frequencies of the G/G, G/A, or A/A genotypes. Eight subjects were homozygous for the less
common A allele, five had IDDM and three were control subjects. Our results suggest that the –30 beta-cell glucokinase promoter
variant is not associated with IDDM. [Diabetologia (1997) 40: 959–962)
Received: 3 February 1997 and in revised form: 29 April 1997 相似文献
20.
T. Kasperska-Czyzyk K. Jedynasty R. R. Bowsher D. L. Holloway I. Stradowska K. Stepień R. Nowaczyk W. Szymczak A. Czyzyk 《Diabetologia》1996,39(7):831-837
Summary The 75-g oral glucose tolerance test was performed in 38 normoglycaemic (World Health Organization criteria) non-diabetic
volunteers, aged 31–40 years, of whom 20 had a non-insulin-dependent diabetic (NIDDM) mother and 18 had an NIDDM father. At
the time of the study the offspring of NIDDM mothers had a somewhat higher body mass index (BMI) (males: 26.5 ± 1.0 (mean
± SEM), females: 27.5 ± 1.5 kg/m2) than the offspring of NIDDM fathers (males: 23.4 ± 0.9, females: 24.2 ± 1.2 kg/m2). There was no difference in the time-course of glycaemia; however the serum concentrations of immunoreactive insulin (IRI),
C-peptide and proinsulin were significantly higher in offspring of NIDDM mothers than in offspring of NIDDM fathers: area
under the curve (AUC) serum IRI: 0.928 ± 0.091 vs 0.757 ± 0.056 nmol · l–1· h–1, p = 0.019; serum C-peptide: 6.379 ± 0.450 vs 4.753 ± 0.242 nmol · l–1· h–1, p = 0.004; serum proinsulin: 172 ± 40 vs 51 ± 7 pmol · l–1· h–1, p = 0.008). Serum IRI correlated with BMI, but C-peptide and proinsulin did not, and after accounting for BMI by covariance
analysis they remained significantly higher in offspring of NIDDM mothers. In this group serum proinsulin was significantly
higher in male than in female offspring (AUC serum proinsulin: 289 ± 68 vs 77 ± 27 pmol · l–1· h–1, P = 0.015). Male offspring of NIDDM mothers also had significantly higher serum triglyceride levels than females of the same
group and than offspring of NIDDM fathers. The offspring (male and female) of NIDDM mothers had slightly lower serum apolipoprotein
A-I levels than the offspring of NIDDM fathers. Significant correlations were found between serum triglycerides, HDL-cholesterol
and apolipoprotein B, and serum concentrations of pancreatic beta-cell peptides, mostly in the offspring of NIDDM mothers;
however, they did not display unequivocal association with gender within this group. The data are consistent with clinical
observations of a greater risk of NIDDM transmission from the mother than from the father, and may suggest that male offspring
are more exposed to this risk than female offspring. [Diabetologia (1996) 39: 831–837]
Received: 2 June 1995 and in final revised form: 19 January 1996 相似文献