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PubMed2006

Improved estimates of net primary productivity from modis satellite data at regional and local scales.

We compared estimates of net primary production (NPP) from the MODIS satellite with estimates from a forest ecosystem process model (PnET-CN) and forest inventory and analysis (FIA) data for forest types of the mid-Atlantic region of the United States. The regional means were similar for the three methods and for the dominant oak-hickory forests in the region. However, MODIS underestimated NPP for less-dominant northern hardwood forests and overestimated NPP for coniferous forests. Causes of inaccurate estimates of NPP by MODIS were (1) an aggregated classification and parameterization of diverse deciduous forests in different climatic environments into a single class that averages different radiation conversion efficiencies; and (2) lack of soil water constraints on NPP for forests or areas that occur on thin or sandy, coarse-grained soil. We developed the "available soil water index" for adjusting the MODIS NPP estimates, which significantly improved NPP estimates for coniferous forests. The MODIS NPP estimates have many advantages such as globally continuous monitoring and remarkable accuracy for large scales. However, at regional or local scales, our study indicates that it is necessary to adjust estimates to specific vegetation types and soil water conditions.

Climate↗
PubMed2000

beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY.

The basic helix-loop-helix (bHLH) family of transcription factors plays an important role in the normal development and function of the endocrine pancreas. Heterozygous mutations in the gene encoding one member of this family, NeuroD1/BETA2, are associated with a monogenic form of diabetes that resembles maturity-onset diabetes of the young (MODY) in many respects. This result prompted us to screen the genes encoding related bHLH transcription factors that are also expressed in pancreatic islets for diabetes-associated mutations. We have screened 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in the NeuroD4/Math-3/ATH-3 gene (NEUROD4). This analysis revealed seven frequent polymorphisms that were not associated with MODY, including five in the 5'-untranslated region (UTR) (-477G/A, -436delA, -324delT, -107insTTTT, and -104T/C [cDNA sequences]) and two in the 3'-UTR (1027C/T and 1076C/A). A missense mutation, K68T (203A/C), was found in a heterozygous state in one MODY subject and two nondiabetic subjects. The results of our study suggest that genetic variation in NEUROD4 is not a common cause of MODY in Japanese.

Basic Helix-Loop-Helix Proteins↗
PubMed2003

[MODY in clinical practice. When and why to consider it?].

It is important to consider in clinical practice the diagnosis of MODY and to characterise the MODY sub-type. Indeed, evolution, clinical consequences and treatment of these forms of diabetes will be different according to the genetic origin of MODY. The main characteristics and consequences in clinical practice of these genetic abnormalities are briefly described, with a particular emphasis on the two most frequent sub-types, MODY-2 and MODY-3, caused by mutations of the enzyme glucokinase and of the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1a) respectively.

Adult↗
PubMed1989

[MODY type diabetes mellitus in children and adolescents].

Nineteen diabetics aged 9 to 18 years with the MODY type were investigated, incl. their families, by the oGTT. Diabetes in the parents was nine times and in siblings four times more frequent than in families of adolescents with IDDM. In parents the manifest form predominated, in siblings PGT. Vertical transmission of diabetes in three consecutive generations was found only in the MODY type (in 35%). Diabetes with the MODY type and their diabetic siblings did not differ significantly as to their mild glucose intolerance (blood sugar level up to 13 mmol/l), and their mild diabetic phenotypes did not differ either. Similarly diabetics with IDDM and their diabetic siblings did not differ substantially as to their severe glucose intolerance (blood sugar level up to 21 mmol/l), and their severe diabetic phenotypes did not differ either. IRI levels revealed five times a hyperinsulinaemic and three times a normal insulinaemic response. Obese diabetics were treated with a reducing diet and physical activity. To non-obese diabetics, if the above procedure was not sufficiently successful, sulphonylurea preparation were also administered. During check-up examinations fasting values and values three hours after a meal lower than 6.1 mmol/l were required. In the course of a four- to ten-year follow up it did not change. Existence of the MODY type already macroangiopathic complications developed; in one diabetic the glucose tolerance improved, in the remainder it did not change. Existence of the MODY type already in adolescents justifies early detection in families with a cumulated incidence of NIDDM and prophylactic procedures ensuring euglycaemia in confirmed diabetics.

Adolescent↗
PubMed2000

Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1alpha (TCF1) promoter region in MODY patients.

Maturity onset diabetes of the young (MODY) is a heterogeneous subtype of type II diabetes mellitus. To date, five MODY genes have been identified. Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are associated with MODY3. In the present work, we implemented the HNF-1alpha promoter region in the screening of MODY-suspect patients and identified seven variants not detected in control subjects. The family was available for the -119delG variant, and segregration between MODY and the variant is observed. Most of these variants are located in highly conserved regions and may alter HNF-1alpha expression through binding alteration of nuclear factors or other mechanisms. We demonstrate by functional studies that the transcriptional activity of the -283A>C and -218T>C variant promoters were 30% and 70% of the wild type activity, respectively. These data suggest that HNF-1alpha promoter variants could be diabetogenic mutations, and emphasize that the accurate HNF-1alpha expression is important for the maintenance of normal pancreatic beta cell function.

5' Untranslated Regions↗
PubMed2001

Mutation in hepatocyte nuclear factor-1alpha is not a common cause of MODY and early-onset type 2 diabetes in Korea.

Maturity-onset diabetes of the young (MODY)-3 with a mutation in hepatocyte nuclear factor (HNF)-1alpha has been identified in most races, but the prevalence of Korean MODY and early-onset type 2 diabetes with a mutation in this gene is unknown. To determine the prevalence of MODY and early-onset type 2 diabetes with the mutation of HNF-1alpha gene in Korea, we analyzed this gene in 69 Korean early-onset type 2 diabetics and in 35 healthy persons using the single-strand conformation polymorphism (SSCP) technique and direct sequencing. We identified one mutation in exon 4 (C900A) in only one of the 69 Korean subjects with early-onset type 2 diabetes; this mutation was silent and did not change the amino acid (Pro300). Additionally, we identified four polymorphisms: S487N, AAC-->AGC, intron 2 (nt -23), intron 7: (nt +7) and intron 9 (nt -24). However, there was no significant difference in frequencies of the four polymorphisms between the type 2 diabetes and control groups. Among type 2 diabetics, codon 487 variant showed no relationship to age at onset, body mass index, fasting blood glucose, HbA1c, lipid profile, basal C-peptide and 2 hour C-peptide. We concluded that this genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and early-onset type 2 diabetes susceptibility in Korea.

Adult↗
PubMed2002

Molecular etiologies of MODY and other early-onset forms of diabetes.

Maturity-onset diabetes of the young (MODY) are monogenic forms of type 2 diabetes that are characterized by an early disease onset, autosomal-dominant inheritance, and defects in insulin secretion. Genetic studies have identified mutations in at least eight genes associated with different forms of MODY. The majority of the MODY subtypes are caused by mutations in transcription factors that include hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, PDX-1, HNF-1 beta, and NEURO-DI/BETA-2. In addition, genetic defects in the glucokinase gene, the glucose sensor of the pancreatic beta cells, and the insulin gene also lead to impaired glucose tolerance. Biochemical and genetic studies have demonstrated that the MODY genes are functionally related and form an integrated transcriptional network that is important for many metabolic pathways.

Age of Onset↗
PubMed1995

A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q.

Maturity-onset diabetes of the young (MODY) is a subtype of non-insulin dependent diabetes mellitus, with early age of onset. MODY is genetically heterogeneous, associated with glucokinase mutations and a locus on chromosome 20q; in about 50% of cases, its genetic background is unknown. We have studied 12 families in which MODY is unlinked to either glucokinase or chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on chromosome 12q, most likely within a 7 centimogran interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this chromosome region in approximately 50% of families in a heterogeneity analysis. These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic beta-cell function.

Adolescent↗
PubMed1995

Variable effects of maturity-onset-diabetes-of-youth (MODY)-associated glucokinase mutations on substrate interactions and stability of the enzyme.

Mutations in the human glucokinase (GK) gene are thought to cause maturity-onset diabetes of youth (MODY) by leading to the production of enzymes with reduced catalytic activities and increased glucose Km values. However, in some cases the diabetic phenotype is more severe than might be predicted from these apparent kinetic effects alone. To determine whether these mutations might also effect other characteristics of the enzyme, nine MODY-associated mutants were expressed as fusion proteins with Schistosoma japonicum glutathione S-transferase (GST) and compared with three wild-type human GK isoforms that were also expressed in the same manner. Three GST-GK isoforms (liver 1, liver 2 and islet) were kinetically indistinguishable from each other and from purified rat liver GK. Noteworthy is a glucose-induced fit effect for the interaction of trinitrophenyl (TNP)-ATP with GST-GK, whereby glucose significantly increased the affinity of TNP-ATP binding to GST-GK without changing the stoichiometry of binding. The nine MODY-associated mutations studied either showed diminished catalytic activity, substrate affinities, allosteric regulation, or stability of the fusion enzyme. We conclude that: (1) Gly261 and Lys414 are important for ATP binding; (2) Val203 may be essential for a glucose-induced fit effect; and (3) the stability of fusion protein may be significantly reduced when Glu300 is replaced by Lys. These results suggest that, in addition to effects on the Km and Vmax. of GK, a decrease in the ATP-binding affinity or stability of the mutated enzyme may also contribute to a reduction of GK activity in individuals with GK-MODY. In the B-cell this would have the effect of blunting glucose-stimulated insulin release, thereby contributing to the diabetic phenotype.

Adenosine Triphosphate↗
PubMed1998

Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period.

Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown. F2 mice were obtained by F1 (diabetic C57BL6 x normal Mus musculus castaneus) crosses. About 20% of the F2 progeny developed diabetes by 2 wk of age, 50% of the progeny were normal at 2 wk and developed diabetes between 5 and 8 wk of age, and the remaining 30% did not develop diabetes. Quantitative trait locus analysis using blood glucose levels of 118 F2 mice at 2 wk of age and 5-8 wk of age located Mody within 3 cM of D7Mit258. Histopathological investigation revealed hypoplastic islets (approximately 33% of that of wild-type mice) and a lower density of beta cells (approximately 20% of wild-type) with a reciprocal dominance of alpha cells (four times that of wild-type) in Mody homozygotes. Electron microscopic observations revealed a specific decrease in the number of insulin secretory granules and a lower density of beta cells. Ratios of insulin to glucagon contents confirmed specific decreases in insulin content: 0.01 for homozygotes, 0.54 for heterozygotes, and 1.11 for wild-type mice on day 14. These results suggest that Mody is involved in both islet growth and beta cell function.

Animals↗
PubMed2003

Validation of Terra-MODIS phytoplankton chlorophyll fluorescence line height. I. Initial airborne lidar results.

The Moderate Resolution Imaging Spectroradiometer (MODIS) aboard the Terra spacecraft contains spectral bands that allow retrieval of solar-induced phytoplankton chlorophyll fluorescence emission radiance. Concurrent airborne laser-induced (and water-Raman normalized) phytoplankton chlorophyll fluorescence data is used to successfully validate the MODIS chlorophyll fluorescence line height (FLH) retrievals within Gulf Stream, continental slope, shelf, and coastal waters of the Middle Atlantic Bight portion of the western North Atlantic Ocean for 11 March 2002. Over the entire approximately 480-km flight line a correlation coefficient of r2 = 0.85 results from regression of the airborne laser data against the MODIS FLH. It is also shown that the MODIS FLH product is not influenced by blue-absorbing chromophoric dissolved organic matter absorption. These regional results strongly suggest that the FLH methodology is equally valid within similar oceanic provinces of global oceans.

Journal Article↗
PubMedDate not supplied

Maturity-onset diabetes of the young (MODY): a new challenge for pediatric diabetologists.

The differential diagnosis of hyperglycemia in childhood and adolescence has to take into consideration early-onset non-insulin-dependent diabetes, defined as maturity onset diabetes of the young (MODY). To date, mutations in genes of five proteins have been shown to cause MODY: glucokinase (MODY2), hepatic nuclear factor-1 alpha (HNF-1 alpha) (MODY3), hepatic nuclear factor-4 alpha (HNF-4 alpha) (MODY1), insulin promoter factor 1 (IPF-1) (MODY4) and hepatic nuclear factor-1 beta (HNF-1 beta) (MODY5), but other MODY genes still await elucidation. Clinical and metabolic heterogeneity of these subtypes of type 2 diabetes need to be defined, as deficiency of each factor has its own phenotype. Pediatric diabetologists should be aware of the increasing importance of MODY as a possible cause of hyperglycemia in children and adolescents. This will allow for the early diagnosis of these metabolic conditions and for the appropriate follow-up and treatment.

Adolescent↗
PubMed1988

Insulin action and insulin secretion in identical twins with MODY. Evidence for defects in both insulin action and secretion.

To evaluate the pathogenetic mechanisms responsible for development of diabetes in the genetically inherited disease maturity-onset diabetes of the young (MODY), we have investigated a pair of identical twins (19 yr old) from a MODY family. One twin had nondiabetic fasting plasma glucose values but impaired glucose tolerance (IGT), whereas the other suffered from frank diabetes (fasting plasma glucose 12.5 mM). Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. Therefore, our aim was to investigate insulin secretion and insulin action in the twins to find these differences and similarities. We found that fasting plasma insulin and C-peptide values were slightly increased in the twins, whereas the responses of insulin and C-peptide to oral glucose tolerance tests (OGTT) and meals were similar in the twins and within normal range. The insulin responses to OGTT were, however, lower than expected from the glucose values, indicating a beta-cell defect. Despite elevated plasma insulin levels, basal hepatic glucose output (HGO) was normal in the IGT twin but increased by 75% in the diabetic twin. The maximally inhibitory effect of insulin on HGO, when estimated at euglycemia, was normal in the IGT twin but reduced by 60% in the diabetic twin. Furthermore, the maximal insulin-mediated glucose uptake in peripheral tissues was reduced by 40% in the diabetic twin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus (NIDDM) associated with autosomal-dominant inheritance. In the RW pedigree, MODY is associated with polymorphic DNA markers on chromosome 20q. To determine the early abnormalities of insulin action and insulin secretion in MODY, we studied nondiabetic members of the RW pedigree with and without the gene marker. Six nondiabetic marker-negative and 5 nondiabetic marker-positive members of the RW pedigree were studied, as were 4 diabetic marker-positive family members. Unrelated, young, healthy subjects served as comparison groups. Insulin action and insulin secretion were assessed with a frequently sampled intravenous glucose tolerance test. Insulin secretion was further assessed during constant glucose infusion by deconvolution of plasma C-peptide and by pulse analysis. The nondiabetic marker-positive group had normal sensitivity to insulin and unimpaired acute insulin response to intravenous glucose (AIRglu). However, the nondiabetic marker-positive group had decreased mean plasma C-peptide concentration and reduced absolute amplitude of insulin secretory oscillations during prolonged glucose infusion. These responses to prolonged glucose infusion were similar to those observed in the diabetic group. No alterations of insulin secretion were observed in the nondiabetic marker-negative family members. Deranged and deficient insulin secretion, and not insulin resistance, appears to be the genetic or primary abnormality that characterizes nondiabetic individuals who are predisposed to MODY in the RW pedigree.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

High prevalence of maturity-onset diabetes of the young (MODY) among Indians.

This article describes the high prevalence of maturity-onset diabetes in the young (MODY) in an Indian clinic population of diabetic patients. MODY appears to be more common among Indians than among Caucasians. Only 27% of MODY patients had definite autosomal-dominant inheritance. In 73% the mode of inheritance was not definite. Microvascular complications were common and macrovascular complications rare. The high prevalence of MODY in this diabetes clinic might suggest an ethnic variation in diabetes.

Adult↗
PubMed2003

[Study on the relationship between Terra-MODIS image and the snail distribution in marshland of Jiangning county, Jiangsu province].

OBJECTIVE: To analyze the relationship between the normalized difference vegetation index (NDVI) and the snail distribution in marshland of Jiangning county in Jiangsu province, and to explore the utility of Terra-MODIS image map in the small scale snail habitats surveillance. METHODS: NDVI were extracted from MODIS image by vector chart of the snail distribution using ArcView 8.1 and ERDAS 8.5 software. The relationship between NDVI and the snail distribution were Investigated using Bivariate correlations and stepwise linear regression. RESULTS: The snail density on marshland was positively correlated with the mean NDVI in the first ten-day of May and the maximum NDVI (N(20max)) in the last ten-day of May. Incidence of pixel with the live snail on marshland was positively correlated with the mean NDVI (N(2mean)) in the first ten-day of May. An equation Y(1) = 0.009 47 x N(20max) (R(2) = 0.73), Y(2) = 0.018 6 x N(2mean) (R(2) = 0.906) was established. CONCLUSION: This study showed that the Terra-MODIS satellite images reflecting the status of the vegetation on marshland in Jiangning county could be applied to the study to supervise the snail habitat. The results suggested that MODIS images could be used to survey the small scale snail habitats on marshland.

Animals↗
PubMed2003

[Maturity-onset diabetes of the young (MODY): the history of its dismemberment].

Type 2 diabetes (T2D) is a complex multifactorial disease. Genetic susceptibility is clearly needed, but in most cases, is not sufficient to induce T2D. Environmental factors are determinant in most patients to develop T2D. Monogenic forms of diabetes such as the maturity-onset diabetes of the young (MODY) represent a model to study the genetic basis of T2D. Studies in MODY individuals and families lead to a genetic definition of MODY subtypes with profound implications for our understanding of gene mutations involved in the development of T2D through our understanding on the major role of these genes and on their transcriptional activity on b-cell development and function; and on the regulation of glucose and insulin metabolism. Our current knowledge on the heterogeneity of MODY diabetes and contribution to our comprehension of the molecular mechanisms involved in T2D are described.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1982

[Chlorpropamide-alcohol flush test in non-insulin-dependent diabetes mellitus in young age (MODY type)].

The chlorpropamide alcohol flush test (CPAF) has been described as a dominantly inherited feature in NIDDM, particularly of young people (MODY-type). Validity and usefulness of the CPAF were analyzed in 40 MODY-patients recruiting from a population study (criteria acc. to Tattersall and Fajans, 1975), 59 first degree relatives (24 diabetics, 35 non-diabetics), 40 NIDDM of maturity onset, 40 IDDM, and 40 healthy controls. The CPAF (single challenge test, placebo control, subjective evaluation by questionnaire acc. to Köbberling, 1980) proved to be positive in only 8 MODY-patients and 5 of diabetic first-degree relatives. In comparison to NIDDM of maturity onset (40/8), IDDM (40/6) and healthy controls (40/2) the frequency of positive CPAF showed no significant differences. Between flushers and non-flushers within the MODY-group no relationship to vascular findings, metabolic and genetic data (including HLA-typing) could be found. It is concluded that the CPAF is a real but rather nonspecific phenomenon unsuitable as a genetic marker.

Adolescent↗