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Phenylketonuria (PKU) is a metabolic disorder that is inherited in an autosomal recessive pattern and is caused by a defect in the hepatic phenylalanine (PA) hydroxylating system. References1.Smith I (1974) Atypical phenylketonuria accompanied by a severe progressive neurological illness unresponsive to dietary treatment. JavaScript is currently disabled, this site works much better if you enable JavaScript in your browser. Except where otherwise noted, this work is licensed under Creative Commons Attribution-NonCommercial 4.0 International License.
IntroductionThe incidence of diabetes, a serious health problem worldwide is increasing dramatically.
ResultsClinical characteristics including age, length of disease, FPG, HbA1c, Insulin, IGF-1, IGFBP-3, Leptin, and BMI in the two groups are presented in Table 1. DiscussionLeptin secretion is influenced by many hormonal and metabolic factors18, 19 but their respective roles in the overall regulation of leptin production have not been fully ascertained. AcknowledgementThis project was supported by the endocrine re-search center, Tehran University of Medical Sciences, grant number E222.
In addition, overweight and obesity results in health disorders in diabetic patients.1 The pa-thogenesis of obesity remains largely unknown, but research on its pathophysiology has recent-ly intensified, following the discovery of leptin.
The length of disease in diabetic patients ranged between 1 to 95 months (mean 70.6 months). Besides a close correlation to BMI, leptin secretion has been suggested to be modulated by insulin, 19 thyroid hormones20 and supply of dietary energy.19, 20 The results of the present study confirm that body composition and insulin variables affect leptin regulation.
The authors are grateful to the personnel of the radio pharmacy lab in the drug applied research center, Tabriz University of Medical Sciences.
Serum leptin concentrations during severe protein-energy malnutrition: correlation with growth parameters and endocrine function. Serum leptin levels in children an adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index. Regulation of development and metabolism of adipose tissue by growth hormone and the insulin-like growth factor system. Relation between plasma leptin and anthropometric and metabolic cova-riates in lean and obese diabetic and hyperlipi-daemic Asian Northern Indian subjects. Plasma leptin is associated with in-sulin resistance independent of age, body mass in-dex, fat mass, lipids, and pubertal development in nondiabetic adolescents.
Insulin sensitivity and se-cretion influence the relationship between growth hormone-binding-protein and leptin.
Serum le-vels of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 in healthy centenarians: relation-ship with plasma leptin and lipid concentrations, insu-lin action, and cognitive function. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-1, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. Relationships be-tween IGF-1 and age, gender, body mass, fat dis-tribution, metabolic and hormonal variables in ob-ese patients.

Relationship of serum leptin concentration with age, gender, and biomed-ical parameters in healthy, non-obese subjects.
Effect of obesity on total and free insu-lin-like growth factor (IGF)-1, and their relation-ship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Interactions between serum leptin, the insulin-like growth factor-I system, and sex, age, anthropometric and body composition va-riables in a healthy population randomly selected. Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sen-sitivity. A twin study for serum leptin, soluble leptin receptor, and free insu-lin-like growth factor-I in pubertal females. Effect of obesity on total and free insulin-like growth factor (IGF-1), and their ralationship to IGF-binding protein (BP)-1,IGFBP-2, IGFBP-3, in-sulin, and growth hormone. However, accumulating evidence suggests that the role of leptin is much broader than that of an antiobesity hormone. We hypothesized that plasma leptin concentrations may be correlated to IGF-1 in type 2 diabetes. Leptin and other variables levels of nondiabetic and diabetic group were compared using the Student's independent samples ttest.
Regarding medication for glucose control, 10 patients used metformin, 4 patients Sulfonylurea, and 10 both drugs; 14 used no medication.
In agreement with results documented by some authors, we found an age related, but not gender related difference in IGF-1 concentrations, both in overweight and obese subjects. During each hydroxylation cycle of these three enzymes, BH4 is oxidized to quininoid dihydrobiopterin (q-BH2), the latter being transformed partly into L-erythro-7, 8-dihydrobiopterin (7,8-BH2).
We measured the concentrations of fasting plasma glucose (FPG), IGF-1, hemoglobin A1C (HbA1c) and insulin like growth factor binding protein-3(IGFBP-3) in both groups. Leptin also affects several neuroendocrine mechanisms.2, 3Leptin, a 16-KD protein secreted from white adipocytes, has been implicated in the relation of food intake5 energy expenditure and whole-body energy balance in rodents and humans. Correlations of leptin levels with the other parameters were evaluated by the Pearson correlation coefficient. FPG was measured by the enzymat-ic glucose oxidase method and the Hb Gold ana-lyzer HPLC was used to measure HbA1C. The expression and secretion of leptin is highly correlated with body fat mass and adipocte size.6 Insulin and cortisol are potent stimulators of leptin expression and the role of other hormones and growth factors in the regulation of leptin expression and se-cretion is coming to light. Exclusion criteria were subjects with known diseases as-sociated with disordered glucose metabolism (e.g. IGF-1 concentrations are markedly reduced in malnutrition and anorexia nervosa, 22 as well as in catabolic states. For de-termination of leptin, IGF-1, IGFBP-3 and insu-lin concentrations, the enzyme linked immuno-sorbent assay (ELISA) method was used. 7, 8 The plasma lev-el of leptin has a positive correlation with body mass index in rodents and humans.

Cushing's disease), pancreatectomy, sub-jects with past or present thyroid dysfunction or those treated with thyroid hormones or current-ly pregnant, subjects on glucose altering medi-cations, including glucocorticoids, thiazides, in-terferon-?, retroviral agents and anti-neoplastic agents; also excluded were subjects with chron-ic disease such as kidney, heart and hepatic dis-eases. Newcastle upon Tyne, 19845.Irons M, Levy HL, O’Flynn ME, Stack CV, Langlais PJ, Butler IJ, Milstien S, Kaufman S (1987) Folinic acid therapy in treatment of dihydropteridine reductase deficiency.
In both groups, mean serum levels of leptin in males, were statistically lower than in females. Subjects with endocrine disease, signifi-cant renal or hepatic disease, and those re-ceiving medication for disordered glucose metabolism, hypertension or hyperlipidemia, were excluded from the study.
Written in-formed consent was obtained from each sub-ject and the institutional review board of Ta-briz University approved the study protocol according to the Declaration of Helsinki. Furthermore, leptin may also be directly involved in the pathophysiology of type 2 diabetes mellitus.
Anthropometric measurements and sampling All individuals were asked to complete a self questionnaire on anthropometric characteristics, general health, smoking, alcohol consumption, and present medications, including hormone replacement, oral hypoglycemic agents and oral contraceptive treatment.
In summary, it is speculated that serum leptin and IGF-1 levels in patients with type 2 diabetes were increased compared to the non-diabetic control group. Thus, leptin most likely plays a role in the pathophysiology of type 2 diabetes mellitus, particularly in obese individuals.
Waist circumference was defined as the smallest girth midway between the lowest rib margin and the iliac crest.
Blood sam-ples were collected (10 mL) after 8-12 hours fasting in a sitting position from the antecu-bital vein.
Sera that were separated imme-diately after centrifugation with 3000 x g for 10 min were stored at -70 °C until the assay for clinical measurements was performed. Laboratory MeasurementsFasting blood glucose (FPG) was measured by the glucose oxidase method (Pars Azmun.
HbA1c was meas-ured in both patients and controls by Hb gold analyzer with high performance liquid chro-matography on reversed phase partition ion exchange chromatography, with the coeffi-cient of variation (CV) below 5%.
Serum lep-tin level was measured by the sandwich and competition kind of ELISA, using recombi-nant human leptin and two special antibodies (IBL. Serum concentrations of insulin like growth factor, after extraction using the ethanol acid method by ELISA (Bio source.
Serum level of IGFBP-3 was meas-ured using ELISA and two special antibodies with high affinity for two different epitopes (Bio source.
Serum levels of insulin were measured by ELISA, using a commercially available kit (Monobind, USA,) including high affinity antibody and special enzyme conjugate.

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