| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Bjorklund, A, et al.
(author)
-
Enhancing effects of long-term elevated glucose and palmitate on stored and secreted proinsulin-to-insulin ratios in human pancreatic islets
- 1999
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 48:7, s. 1409-1414
-
Journal article (peer-reviewed)abstract
- Relative hypersecretion of proinsulin is a feature of type 2 diabetes. We investigated to what extent this feature can be induced in human pancreatic islets by elevated glucose or fatty acids, two major abnormalities of the diabetic state. A 48-h culture period with 27 mmol/l glucose increased the intraislet proinsulin-to-insulin (PI/I) ratio 5.0-fold, owing to preferential decrease of insulin. The PI/I ratio in culture medium was enhanced 1.9-fold versus islets cultured with 5.5 mmol/l glucose. This effect of elevated glucose persisted after normalization of glucose levels: during 60-min postculture incubations at a basal glucose concentration (3.3 mmol/l), the PI/I ratio of secretion increased 4.9-fold. The ratio was also increased (14-fold) after renewed postculture stimulation with 16.7 mmol/l glucose. Diazoxide was added to culture medium to block glucose-induced insulin secretion and thus investigate the importance of overstimulation. In cultures at 27 mmol/l glucose, the presence of diazoxide decreased the PI/I ratio of islet contents by 76%, the accumulated secretion to culture medium by 70%, and the release at 3.3 or 16.7 mmol/l glucose during postculture incubations by 85 and 86%, respectively. None of these PI/I-decreasing effects of diazoxide were reproduced during or after coculture with 5.5 mmol/l glucose. Culture with 0.2 mmol/l palmitate and 5.5 mmol/l glucose decreased islet contents of proinsulin and insulin and increased the secreted products in culture media without affecting PI/I ratios. During postculture conditions, however, prior palmitate culture enhanced the PI/I ratio of release at 3.3 mmol/l glucose (from 2.2 +/- 0.4 to 5.4 +/- 0.9%, P < 0.05). Culture with palmitate together with 27 mmol/l glucose decreased islet contents of proinsulin and insulin and further enhanced intraislet PI/I ratios (from 9.3 +/- 1.1 to 13.4 +/- 2.5%, P < 0.05). However, palmitate failed to affect PI/I ratios in culture medium. In contrast, in postculture incubations at 3.3 mmol/l glucose, prior palmitate culture further elevated the PI/I ratio of secretion (from 10.8 +/- 1.2 after previous 27 mmol/l glucose alone to 13.9 +/- 2.8% after palmitate and glucose, P < 0.05). We conclude that 1) long-term exposure of human islets to elevated glucose leads to preferential secretion of proinsulin, and this effect persists also after glucose normalization; 2) the glucose effect appears secondary to depletion of mature insulin granules; and 3) elevated fatty acids influence PI/I ratios of secretion by mechanisms that are, in part, incongruous with an over-stimulation effect.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Carlsson, S, et al.
(author)
-
Low birth weight, family history of diabetes, and glucose intolerance in Swedish middle-aged men
- 1999
-
In: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 22:7, s. 1043-1047
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the association between low birth weight and glucose intolerance in relation to family history of diabetes. RESEARCH DESIGN AND METHODS: We conducted a population-based cross-sectional study of 2,237 men born in 1938-1957 in four municipalities in the outskirts of Stockholm, 50% of whom had a family history of diabetes (at least one first-degree or two second-degree relatives with diabetes). Oral glucose tolerance testing detected 35 cases of type 2 diabetes, 102 cases of impaired glucose tolerance, and 57 cases of impaired fasting glucose. RESULTS: In subjects without a family history of diabetes, low (< or = 3,000 g) birth weight was associated with an odds ratio of 2.3 (95% confidence intervals = 0.4-14.4) for diabetes, 1.8 (0.7-4.3) for impaired glucose tolerance, and 3.3 (1.0-10.4) for impaired fasting glucose. In subjects with a family history of diabetes, the corresponding figures were approximately similar, except for diabetes, for which the odds ratio was 5.4 (2.0-14.9). For men with low birth weight in combination with a family history of diabetes, the odds ratio was 10.9 (2.9-41.2) for diabetes, 2.4 (1.1-5.6) for impaired glucose tolerance, and 5.9 (2.1-16.3) for impaired fasting glucose. CONCLUSIONS: This study indicated that low birth weight is associated with type 2 diabetes, impaired glucose tolerance, and impaired fasting glucose in men. This finding was most pronounced in subjects with diabetes in the family, but it was also indicated in those without a family history of diabetes. Men with the combination of low birth weight and family history of diabetes seem to be at particularly high risk of developing type 2 diabetes.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Persson, PG, et al.
(author)
-
Food frequency questionnaire versus 7-day weighed dietary record information on dietary fibre and fat intake in middle-aged Swedish men
- 1998
-
In: Scandinavian journal of social medicine. - : SAGE Publications. - 0300-8037. ; 26:1, s. 75-80
-
Journal article (peer-reviewed)abstract
- To study the magnitude of agreement between a short self-administered food frequency questionnaire and a 7-day weighed dietary record regarding the consumption of fibre and fat, we collected information from 92 randomly selected middle-aged Swedish men. The participants first recorded all foods and drinks consumed over seven consecutive days by means of a digital scale. One month after the 7-day weighed record had been completed, a self-administered food frequency questionnaire on habitual consumption of foods containing fibre or fat during the preceding month was sent to the subjects. The 20 largest contributors of fibre and fat in the diet accounted for 71% and 52% of the total intake, respectively, based on the 7-day weighed record. The estimated mean consumption of fibre was 19.0 grams per day based on the 7-day weighed record and 18.3 grams per day based on the food frequency questionnaire. Corresponding estimated mean consumption of fat was 88.6 grams per day versus 46.9 grams per day. Men with high physical activity and low BMI, respectively, had higher intake of fibre and fat. These differences were seen for both dietary measurement methods but were more marked using the 7-day weighed record. The agreement between methods for each individual was also assessed. Based on five categories of fibre consumption, 61% of the respondents in the highest quintile according to the 7-day weighed record were classified in one of the two highest quintiles according to the food frequency questionnaire. The corresponding figure for fat intake was 56%. We conclude that the short self-administered food frequency questionnaire used in the present study can assess the absolute intake of fibre, but not of fat, with good precision. Also, the ranking of indiviudals in broad categories of consumption of fibre and fat was not largely misclassified based on this short questionnaire.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Zhou, YP, et al.
(author)
-
A fatty acid-induced decrease in pyruvate dehydrogenase activity is an important determinant of beta-cell dysfunction in the obese diabetic db/db mouse
- 1996
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 45:5, s. 580-586
-
Journal article (peer-reviewed)abstract
- We studied the effects of fatty acid oxidation on insulin secretion of db/db mice and underlying molecular mechanisms of these effects. At 2–3 months of age, db/db mice were markedly obese, hyperglycemic, and hyperinsulinemic. Serum free fatty acid (FFA) levels were increased in 2-month-old (1.5 ± 0.1 vs. 1.1 ± 0.1 mmol/l, P < 0.05) and 3-month-old (1.9 ± 0.1 vs. 1.2 ± 0.1 mmol/l, P < 0.01) mice compared with the age and sex-matched db/+ mice serving as controls. Glucose-induced insulin release from db/db islets was markedly decreased compared with that from db/+ islets and was specifically ameliorated (by 54% in 2-month-old and 38% in 3-month-old mice) by exposure to a carnitine palmitoyltransferase I inhibitor, etomoxir (1 μmol/l). Etomoxir failed to affect the insulin response to α-ketoisocaproate. The effect of etomoxir on glucose-induced insulin release was lost after culturing db/db islets in RPMI medium containing 22 mmol/l glucose but no fatty acid. Culture of db/+ islets with 0.125 mmol/l palmitate led to a decrease in glucose-induced insulin secretion, which was partially reversible by etomoxir. Both islet glucose oxidation and the ratio of glucose oxidation to utilization were decreased in db/db islets. Etomoxir significantly enhanced glucose oxidation by 60% and also the ratio of oxidation to glucose utilization (from 27 ± 2.5 to 37 ±3.0%, P < 0.05). Pyruvate dehydrogenase (PDH) activity was decreased in islets of db/db mice (75 ±4.2 vs. 91 ± 2.9 nU/ng DNA, P < 0.01), whereas PDH kinase activity was increased (rate of PDH inactivation −0.25 ± 0.02 vs. −0.11 ± 0.02/min, P < 0.01). These abnormalities were partly but not wholly reversed by a 2-h preexposure to etomoxir. In conclusion, elevated FFA levels in the db/db mouse diminish glucose-induced insulin secretion by a glucose–fatty acid cycle in which fatty acid oxidation inhibits glucose oxidation by decreasing PDH activity and increasing PDH kinase activities.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
