| 51. |
- Hull, Rebecca L, et al.
(författare)
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Islet amyloid : A critical entity in the pathogenesis of type 2 diabetes
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:8, s. 3629-3643
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Tidskriftsartikel (refereegranskat)abstract
- Islet amyloid deposition is a pathogenic feature of type 2 diabetes, and these deposits contain the unique amyloidogenic peptide islet amyloid polypeptide. Autopsy studies in humans have demonstrated that islet amyloid is associated with loss of β-cell mass, but a direct role for amyloid in the pathogenesis of type 2 diabetes cannot be inferred from such studies. Animal studies in both spontaneous and transgenic models of islet amyloid formation have shown that amyloid forms in islets before fasting hyperglycemia and therefore does not arise merely as a result of the diabetic state. Furthermore, the extent of amyloid deposition is associated with both loss of β-cell mass and impairment in insulin secretion and glucose metabolism, suggesting a causative role for islet amyloid in the islet lesion of type 2 diabetes. These animal studies have also shown that β-cell dysfunction seems to be an important prerequisite for islet amyloid formation, with increased secretory demand from obesity and/or insulin resistance acting to further increase islet amyloid deposition. Recent in vitro studies suggest that the cytotoxic species responsible for islet amyloid-induced β-cell death are formed during the very early stages of islet amyloid formation, when islet amyloid polypeptide aggregation commences. Interventions to prevent islet amyloid formation are emerging, with peptide and small molecule inhibitors being developed. These agents could thus lead to a preservation of β-cell mass and amelioration of the islet lesion in type 2 diabetes.
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| 52. |
- Hulthén, L, et al.
(författare)
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GH is needed for the maturation of muscle mass and strength in adolescents.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 86:10, s. 4765-70
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Tidskriftsartikel (refereegranskat)abstract
- The postpubertal period and the early years of adulthood may be of importance for continuing tissue maturation of importance in adulthood and aging. An example of this is the peak bone mass. This study has evaluated the importance of GH for lean mass and muscle strength in adolescents and young adults. GH treatment was discontinued in 40 adolescents aged 16-21 yr with GH deficiency of childhood onset. Measurements of isometric and isokinetic knee-extensor and flexor strength, handgrip strength, lean body mass, fat-free mass, and total body nitrogen were performed annually for 2 yr. Two hundred fifty healthy adolescents were randomly selected for prospective measurements of lean mass and handgrip strength between the ages of 17 and 21 yr. In the adolescents with continuing GH deficiency, lean body mass decreased, compared with the patients defined as having sufficient endogenous GH. The isometric strength in knee flexors increased in the sufficient endogenous GH group and was unchanged in the GH deficiency group during the 2 yr off GH treatment (between group, P < 0.05). The mean and peak handgrip strength increased on average by 9-15% in the group with sufficient endogenous GH and was unchanged in those with GH deficiency (P < 0.05). Lean body mass and handgrip strength (both, P < 0.001) increased in both the healthy boys and girls who were followed for 4 yr with a more marked increase in the boys. The mean increase in handgrip between the age of 17 and 21 yr was 7-9%. The increased lean mass and improved muscle performance seen in healthy adolescents did not occur in adolescents with GH deficiency. These findings suggest that GH is of importance for the maturation of lean mass and muscle strength in adolescents and young adults.
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| 53. |
- Jacobson, Peter, 1962, et al.
(författare)
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Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 87:10, s. 4442-6
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of mutations within and in the flanking regions of the gene encoding the melanocortin 4 receptor was investigated in severely obese and normal-weight subjects from the Swedish Obese Subjects study, the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family study, and a Memphis cohort. A total of 433 white and 95 black subjects (94% females) were screened for mutations by direct sequencing. Three previously described missense variants and nine novel (three missense, six silent) variants were detected. None of them showed significant association with obesity or related phenotypes. In addition, two novel deletions were found in two heterozygous obese women: a -65_-64delTG mutation within the 5' noncoding region and a 171delC frameshift mutation predicted to result in a truncated nonfunctional receptor. No pathogenic mutations were found among obese blacks or nonobese controls. Furthermore, none of the null mutations found in other populations was present in this sample. In conclusion, our results do not support the prevailing notion that sequence variation in the melanocortin 4 receptor gene is a frequent cause of human obesity.
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| 54. |
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| 55. |
- Jansson, Nina, 1976, et al.
(författare)
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Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments.
- 2003
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:3, s. 1205-11
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Tidskriftsartikel (refereegranskat)abstract
- The activity and expression of placental nutrient transporters are primary determinants for the supply of nutrients to the fetus, and these nutrients in turn regulate fetal growth. We developed an experimental system to assess amino acid uptake in single primary villous fragments to study hormonal regulation of the amino acid transporter system A in term human placenta. Validation of the method, using electron microscopy and studies of hormone production, indicated that fragments maintained ultrastructural and functional integrity for at least 3 h. The activity of system A was measured as the Na(+)-dependent uptake of methylaminoisobutyric acid (MeAIB), and the effect of 1 h incubation in various hormones was investigated. Uptake of MeAIB into villous fragments in the presence of Na(+) was linear up to at least 30 min. Insulin (300 ng/ml, n = 14) increased system A activity by 56% (P < 0.05). This effect was also present at insulin concentrations in the physiological range (+47% at 0.6 ng/ml, n = 10, P < 0.05). Leptin (500 ng/ml, n = 14) increased Na(+)-dependent MeAIB uptake by 37% (P < 0.05). System A activity increased in a concentration-dependent fashion in response to leptin (n = 10). However, neither epidermal GF (600 ng/ml), cortisol (340 ng/ml), nor GH (500 ng/ml) altered system A activity significantly (n = 14). We conclude that primary single isolated villous fragments can be used in studies of hormonal regulation of nutrient uptake into the syncytiotrophoblast. These data suggest that leptin regulates system A, a key amino acid transporter.
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| 56. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:4, s. 1743-9
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Tidskriftsartikel (refereegranskat)abstract
- Although sodium retention and volume expansion occur during GH administration, blood pressure is decreased or unchanged. The aim was to study the effect of short- and long-term GH replacement in adults on sodium balance, renal hemodynamics, and blood pressure. Ten adults with severe GH deficiency were included into a 7-d, randomized, placebo-controlled, cross-over trial followed by 12 months of open GH replacement. All measurements were performed under metabolic ward conditions. Extracellular water (ECW) was determined using multifrequency bioelectrical impedance analysis. Renal plasma flow and glomerular filtration rate were assessed using renal paraminohippurate and Cr(51) EDTA clearances, respectively. Renal tubular sodium reabsorption was assessed using lithium clearance. Plasma renin activity (PRA), plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptides and brain natriuretic peptides (BNP) and 24-h urinary norepinephrine excretion were measured. Seven days of GH treatment decreased urinary sodium excretion. Lithium clearance as a marker of proximal renal tubular sodium reabsorption was unaffected by GH treatment. ECW was increased after both short- and long-term treatment. This increase was inversely correlated to the decrease in diastolic blood pressure (r = -0.70, P = 0.02) between baseline and 12 months. Short-term treatment increased PRA and decreased BNP. The increase in PRA correlated with an increase in 24-h urinary norepinephrine excretion (r = 0.77, P < 0.01). Glomerular filtration rate and renal plasma flow did not change during treatment. The sodium- and water-retaining effect of GH takes place in the distal nephron. The sustained increase in ECW in response to GH is associated with an unchanged or decreased blood pressure. This together with unchanged or decreased atrial natriuretic peptides and BNP may prevent pressure-induced escape of sodium.
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| 57. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:5, s. 2046-52
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight women, aged 25-65 yr, with androgen deficiency due to hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized, placebo-controlled, double blind study, followed by a 6-month open treatment period. The administration of DHEA raised the serum levels of DHEAS to normal age-related reference ranges and increased androstenedione and T to subnormal levels. Androgen effects on skin and/or pubic and/or axillary hair were observed in 84% (32 of 38) of the women after all received 6 months of DHEA treatment. No such effects were observed after the placebo treatment. These effects after 6 months were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03), androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages of partners who reported improved alertness, stamina, and initiative by their spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and 11%, respectively, in the placebo group (P < 0.05). According to the partners, sexual relations tended to improve compared with placebo (P = 0.06). After 6 months of treatment, increased sexual interest or activity was reported by 50% of the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking placebo (P = NS). Compared with levels after placebo administration, high density lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum concentrations of IGF-I, serum markers of bone metabolism, and bone density did not change. In conclusion, oral administration of a low dose of DHEA to adult hypopituitary women induced androgen effects on skin and axillary and pubic hair as well as changes in behavior, with only minor effects on metabolism.
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| 58. |
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| 59. |
- Johanson, Else H, et al.
(författare)
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Fat distribution, lipid accumulation in the liver, and exercise capacity do not explain the insulin resistance in healthy males with a family history for type 2 diabetes.
- 2003
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:9, s. 4232-8
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Tidskriftsartikel (refereegranskat)abstract
- To explore the mechanisms for the insulin resistance associated with a family history of type 2 diabetes, we studied 16 healthy men with at least two first-degree relatives with type 2 diabetes and 16 control subjects without known heredity. They were pair-wise matched for age, body mass index, and fasting triglycerides and underwent an oral glucose tolerance test, iv glucose infusion to measure the early insulin secretion, euglycemic hyperinsulinemic clamp, computed tomography scan, 7-d food record, and a cardiopulmonary exercise test to measure peak oxygen uptake. Insulin sensitivity index was 30% lower (P = 0.02) in relatives, compared with controls, but fasting and 2-h blood glucose and first-phase insulin secretion were similar. There were no differences in mean fasting free fatty acid levels, amount of sc or visceral adipose tissue, or fat accumulation in the liver. Dietary intake and peak oxygen uptake were also similar. However, multiple regression analysis of both groups showed that fat in the liver and physical capacity were, like known heredity for type 2 diabetes, independent predictors of insulin sensitivity. Thus, lipid accumulation in the liver and physical capacity are related to insulin sensitivity, but neither of these factors nor the amount and distribution of the body fat can explain the insulin resistance associated with a family history for type 2 diabetes.
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| 60. |
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