Biliopancreatic Limb Length of Small Intestinal Bypass in Non-obese Goto-Kakizaki (GK) Rats Correlates with Gastrointestinal Hormones, Adipokines, and Improvement in Type 2 Diabetes

2021 ◽  
Author(s):  
Qiwei Zhang ◽  
Zhi Hong ◽  
Jieyao Zhu ◽  
Chao Zeng ◽  
Zhen Tang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastrointestinal Hormones ◽  
Limb Length ◽  
Intestinal Bypass ◽  
Gk Rats ◽  
Biliopancreatic Limb ◽  
Small Intestinal ◽  
Biliopancreatic Limb Length

scholarly journals The Effect of Standard versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients with Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass. The Long-Limb study

2020 ◽  
Author(s):  
Alexander Dimitri Miras ◽  
Anna Kamocka ◽  
Belén Pérez-Pevida ◽  
Sanjay Purkayastha ◽  
Krishna Moorthy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Mechanistic Study ◽  
Intestinal Bypass ◽  
Distal Small Intestine ◽  
Time To Peak ◽  
Biliopancreatic Limb

Objective <p>Roux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.</p> <p>Research Design and Methods</p> <p>Fifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.</p> <p>Results</p> <p>Both groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. </p> <p>Conclusion</p> The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

scholarly journals The Effect of Standard versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients with Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass. The Long-Limb study

2020 ◽  
Author(s):  
Alexander Dimitri Miras ◽  
Anna Kamocka ◽  
Belén Pérez-Pevida ◽  
Sanjay Purkayastha ◽  
Krishna Moorthy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Mechanistic Study ◽  
Intestinal Bypass ◽  
Distal Small Intestine ◽  
Time To Peak ◽  
Biliopancreatic Limb

Objective <p>Roux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.</p> <p>Research Design and Methods</p> <p>Fifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.</p> <p>Results</p> <p>Both groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. </p> <p>Conclusion</p> The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes

Diabetes ◽  
1999 ◽  
Vol 48 (4) ◽  
pp. 927-932 ◽  
Author(s):  
Y. Ihara ◽  
S. Toyokuni ◽  
K. Uchida ◽  
H. Odaka ◽  
T. Tanaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Gk Rats

scholarly journals Effects of Vildagliptin and Metformin on Blood Pressure and Heart Rate Responses to Small Intestinal Glucose in Type 2 Diabetes

Diabetes Care ◽  
2017 ◽  
Vol 40 (5) ◽  
pp. 702-705 ◽  
Author(s):  
Tongzhi Wu ◽  
Laurence G. Trahair ◽  
Tanya J. Little ◽  
Michelle J. Bound ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Heart Rate ◽  
Small Intestinal

scholarly journals Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue

2019 ◽  
Vol 126 (3) ◽  
pp. 626-637 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Matthew T. Lewis ◽  
Jonathan D. Kasper ◽  
Paul D. Chantler ◽  
Robert W. Wiseman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Structure Function ◽  
Vascular Structure ◽  
Gk Rats ◽  
The Impact

Despite extensive investigation into the impact of metabolic disease on vascular function and, by extension, tissue perfusion and organ function, interpreting results for specific risk factors can be complicated by the additional risks present in most models. To specifically determine the impact of type 2 diabetes without obesity on skeletal muscle microvascular structure/function and on active hyperemia with elevated metabolic demand, we used 17-wk-old Goto-Kakizaki (GK) rats to study microvascular function at multiple levels of resolution. Gracilis muscle arterioles demonstrated blunted dilation to acetylcholine (both ex vivo proximal and in situ distal arterioles) and elevated shear (distal arterioles only). All other alterations to reactivity appeared to reflect compromised endothelial function associated with increased thromboxane (Tx)A2 production and oxidant stress/inflammation rather than alterations to vascular smooth muscle function. Structural changes to the microcirculation of GK rats were confined to reduced microvessel density of ~12%, with no evidence for altered vascular wall mechanics. Active hyperemia with either field stimulation of in situ cremaster muscle or electrical stimulation via the sciatic nerve for in situ gastrocnemius muscle was blunted in GK rats, primarily because of blunted functional dilation of skeletal muscle arterioles. The blunted active hyperemia was associated with impaired oxygen uptake (V̇o2) across the muscle and accelerated muscle fatigue. Acute interventions to reduce oxidant stress (TEMPOL) and TxA2 action (SQ-29548) or production (dazmegrel) improved muscle perfusion, V̇o2, and muscle performance. These results suggest that type 2 diabetes mellitus in GK rats impairs skeletal muscle arteriolar function apparently early in the progression of the disease and potentially via an increased reactive oxygen species/inflammation-induced TxA2 production/action on network function as a major contributing mechanism. NEW & NOTEWORTHY The impact of type 2 diabetes mellitus on vascular structure/function remains an area lacking clarity. Using diabetic Goto-Kakizaki rats before the development of other risk factors, we determined alterations to vascular structure/function and skeletal muscle active hyperemia. Type 2 diabetes mellitus reduced arteriolar endothelium-dependent dilation associated with increased thromboxane A2 generation. Although modest microvascular rarefaction was evident, there were no other alterations to vascular structure/function. Skeletal muscle active hyperemia was blunted, although it improved after antioxidant or anti-thromboxane A2 treatment.

scholarly journals Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions

2018 ◽  
Vol 237 (1) ◽  
pp. R1-R17 ◽  
Author(s):  
Martin Haluzík ◽  
Helena Kratochvílová ◽  
Denisa Haluzíková ◽  
Miloš Mráz
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Therapeutic Option ◽  
Gastrointestinal Hormones ◽  
Less Invasive ◽  
Treatment Of Diabetes ◽  
Endoscopic Methods ◽  
Diabetes And Obesity

Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying pathologies such as obesity, arterial hypertension and dyslipidemia represents one of the most important challenges of current medicine. Despite intensive efforts, high percentage of patients with type 2 diabetes does not achieve treatment goals and struggle with increasing body weight and poor glucose control. While novel classes of antidiabetic medications such as incretin-based therapies and gliflozins have some favorable characteristics compared to older antidiabetics, the only therapeutic option shown to substantially modify the progression of diabetes or to achieve its remission is bariatric surgery. Its efficacy in the treatment of diabetes is well established, but the exact underlying modes of action are still only partially described. They include restriction of food amount, enhanced passage of chymus into distal part of small intestine with subsequent modification of gastrointestinal hormones and bile acids secretion, neural mechanisms, changes in gut microbiota and many other possible mechanisms underscoring the importance of the gut in the regulation of glucose metabolism. In addition to bariatric surgery, less-invasive endoscopic methods based on the principles of bariatric surgery were introduced and showed promising results. This review highlights the role of the intestine in the regulation of glucose homeostasis focusing on the mechanisms of action of bariatric and especially endoscopic methods of the treatment of diabetes. A better understanding of these mechanisms may lead to less invasive endoscopic treatments of diabetes and obesity that may complement and widen current therapeutic options.

scholarly journals DO H. PYLORI STATUS AND SMALL INTESTINAL BACTERIAL OVERGROWTH DETERMINE THE CLINICAL COURSE OF CHRONIC ACTIVE GASTRITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS?

2020 ◽  
Vol 73 (6) ◽  
pp. 1223-1228
Author(s):  
Tetiana O. Radionova ◽  
Igor M. Skrypnyk ◽  
Ganna S. Maslova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Epigastric Pain ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Postprandial Fullness ◽  
Chronic Active Gastritis ◽  
Intestinal Bacterial Overgrowth ◽  
Small Intestinal

The aim: To define clinical peculiarities of chronic active gastritis in patients with type 2 diabetes mellitus (T2DM) considering Helicobacter pylori (HP) status and small intestinal bacterial overgrowth (SIBO). Materials and methods: 172 patients with chronic active gastritis were enrolled in the study, 92 out of them had concomitant T2DM. Symptoms were collected with the questionnaire, HP infection was diagnosed with stool antigen test, SIBO was assessed with glucose hydrogen breath test. Results: 87.5% (n=70) patients with chronic gastritis without DM had epigastric pain, however those with T2DM reported pain only in 41.3% (n=38) cases. Other symptoms included: nausea, bloating, early satiety, postprandial fullness, heartburn, belching and vomiting. HP infection in patients with chronic gastritis and concomitant T2DM is significantly associated with symptoms of epigastric pain (OR=2.78, 95%CI 0.92-8.41), bloating (OR=3.92, 95%CI 1.40-10.99), nausea (OR=2.32, 95%CI 0.85-0.6.30), postprandial fullness (OR=1.45, 95%CI 0.54-3.87) and belching (OR=1.01, 95%CI 0.32-3.16), whereas SIBO – with bloating (OR=8.82, 95%CI 2.88-27.01), nausea (OR=5.15, 95%CI 1.88-14.10) and belching (OR=2.53, 95%CI 0.67-9.52). Conclusions: Patients with T2DM and chronic active gastritis report epigastric pain significantly less than non-diabetics. HP infection probably plays a prominent role in development of epigastric pain in patients with T2DM. Additionally, HP is linked to SIBO, which may lead to bloating, belching and nausea onset.

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