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- Edholm, T., et al.
(författare)
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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1191-e315
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Tidskriftsartikel (refereegranskat)abstract
- Background Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. Methods Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg−1 min−1, n = 8), GLP-1 (0.75 pmol kg−1 min−1, n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin. Key Results Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg−1 min−1 decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg−1 min−1 decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg−1 min−1 increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05–0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). Conclusion & Inferences The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
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- Ostenson, CG, et al.
(författare)
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High consumption of smokeless tobacco ("snus") predicts increased risk of type 2 diabetes in a 10-year prospective study of middle-aged Swedish men
- 2012
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 40:8, s. 730-737
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Cigarette smoking increases the risk of type 2 diabetes (T2D). In Sweden and the US, people shift from smoking cigarettes to smokeless tobacco, i.e. oral moist snuff, “snus”, to attain harm-reduction. There are limited and conflicting data as to whether snus increases the risk of T2D. The present study investigated if snus use predicts the risk of T2D incidence. Methods: This is a prospective population-based study where middle-aged Swedish men ( n=2,383), without previously diagnosed T2D, were investigated with oral glucose tolerance test (OGTT) at baseline in 1992–94 and at follow-up 10 years later. Odds ratios (ORs) for newly diagnosed T2D at follow-up were assessed among those using snus, or cigarettes, at both baseline and follow-up, adjusted for major confounders. Results: The OR for T2D was not significantly increased in the whole group of snus users. However, the risk of diabetes increased with increasing weekly snus consumption; ORs (CIs) for >four boxes of snus/week were 2.1 (CI 0.9–4.9), and for >five boxes/week 3.3 (CI 1.4–8.1). For comparison, men smoking at baseline and still smoking at follow-up had an increased risk of diabetes compared with never smokers, OR 1.5 (CI 0.8–3.0), most evident for those smoking >15 cigarettes per day, OR 2.4 (CI 1.0–5.8). Tobacco use was associated with estimations of low insulin response (OGTT), but not low insulin sensitivity (HOMA). Conclusions: High consumption of snus, like smoking, predicts risk of developing T2D. This should be considered when seeking harm-reduction by changing from use of cigarettes to snus. T2D risk from tobacco use may be mediated by effects on beta-cell function.
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- Yue, JTY, et al.
(författare)
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Amelioration of hypoglycemia via somatostatin receptor type 2 antagonism in recurrently hypoglycemic diabetic rats
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:7, s. 2215-2222
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Tidskriftsartikel (refereegranskat)abstract
- Selective antagonism of somatostatin receptor type 2 (SSTR2) normalizes glucagon and corticosterone responses to hypoglycemic clamp in diabetic rats. The purpose of this study was to determine whether SSTR2 antagonism (SSTR2a) ameliorates hypoglycemia in response to overinsulinization in diabetic rats previously exposed to recurrent hypoglycemia. Streptozotocin diabetic rats (n = 19), previously subjected to five hypoglycemia events over 3 days, received an insulin bolus (10 units/kg i.v.) plus insulin infusion (50 mU/kg/min i.v.) until hypoglycemia ensued (≤3.9 mmol/L) (experimental day 1 [Expt-D1]). The next day (Expt-D2), rats were allocated to receive either placebo treatment (n = 7) or SSTR2a infusion (3,000 nmol/kg/min i.v., n = 12) 60 min prior to the same insulin regimen. On Expt-D1, all rats developed hypoglycemia by ∼90 min, while on Expt-D2, hypoglycemia was attenuated with SSTR2a treatment (nadir = 3.7 ± 0.3 vs. 2.7 ± 0.3 mmol/L in SSTR2a and controls, P < 0.01). Glucagon response to hypoglycemia on Expt-D2 deteriorated by 20-fold in the placebo group (P < 0.001) but improved in the SSTR2a group (threefold increase in area under the curve [AUC], P < 0.001). Corticosterone response deteriorated in the placebo-treated rats on Expt-D2 but increased twofold in the SSTR2a group. Catecholamine responses were not affected by SSTR2a. Thus, SSTR2 antagonism after recurrent hypoglycemia improves the glucagon and corticosterone responses and largely ameliorates insulin-induced hypoglycemia in diabetic rats.
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- Zhang, DY, et al.
(författare)
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Genetic and functional effects of membrane metalloendopeptidase on diabetic nephropathy development
- 2011
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 34:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Vasopeptidase as an agent inhibits membrane metalloendopeptidase (MME, also known as neutral endopeptidase). MME is widely distributed in the body and particularly abundant in the kidney. The <i>MME </i>gene is located on chromosome 3q25.1 within a linkage region for diabetic nephropathy (DN). The present study aims to evaluate the genetic and functional effects of MME in the development of DN. <i>Methods:</i> A case-control genetic study of the<i> MME</i> gene in type 1 diabetes (T1D) patients with and without DN (n = 578/599) was performed. All subjects were selected from the Genetics of Kidneys in Diabetes study. Genotyping was performed with TagMan allelic discrimination. <i>Mme </i>mRNA and protein expression levels in kidney tissues of db/db mice at the ages of 5, 12 and 26 weeks were analyzed with TaqMan real-time RT-PCR and Western blot. <i>Results:</i> The haplotype A-C constructed with single nucleotide polymorphisms (SNPs) rs3796268A/G and rs3773885C/T in the <i>MME</i> gene was found to be associated with DN (p = 0.015, OR = 1.33, 95% CI 1.05–1.68) in female T1D patients. Further analyses of renal traits in T1D patients with DN and end-stage renal disease according to the genotypes of SNP rs3773885 indicated that the C allele carriers had higher serum creatinine levels compared to the subjects carrying T allele in both females and males. <i>Mme </i>expression at mRNA and protein levels was upregulated in kidneys of db/db mice at the ages of 12 and 26 weeks (p = 0.017 and <0.001) but not at the age of 5 weeks compared to the controls. <i>Conclusions:</i> The present study provides the first evidence that <i>MME </i>has genetic and biological effects on the development of DN, and suggests that the inhibition of <i>MME </i>expression in the kidney with the agent of vasopeptidase may be a useful therapeutic approach for this disease.
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