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Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals.

ABSTRACT: Recent reports have established the notion that many patients with longstanding type 1 diabetes (T1D) possess a remnant population of insulin-producing beta cells. It remains questionable, however, whether these surviving cells can physiologically sense and respond to glucose stimuli.Frozen pancreatic sections from non-diabetic donors (n=8), type 2 diabetic patients (n=4), islet autoantibody-positive non-diabetic patients (n=3), type 1 diabetic patients (n=10) and one case of gestational diabetes were obtained via the network for Pancreatic Organ Donors. All longstanding T1D samples were selected based on the detection of insulin-producing beta cells in the pancreas by immunohistochemistry. RNA was isolated from all sections followed by cDNA preparation and quantitative real-time polymerase chain reaction for insulin, glucose transporter 1 (GLUT1), GLUT2 and GLUT3. Finally, immunofluorescent staining was performed on consecutive sections for all four of these markers and a comparison was made between the expression of GLUT2 in humans versus NOD mice.In contrast to islets from the most widely used T1D model, the NOD mouse, human islets predominantly express GLUT1 and, to a much lesser extent, GLUT3 on their surface instead of GLUT2. Relative expression levels of these receptors do not significantly change in the context of the various (pre-)diabetic conditions studied. Moreover, in both species preservation of GLUT expression was observed even under conditions of substantial leucocyte infiltration or decades of T1D duration.These data suggest that despite being subjected to multiple years of physiological stress, the remaining beta-cell population in longstanding T1D patients retains a capacity to sense glucose via its GLUTs.

SUBMITTER: Coppieters KT

PROVIDER: S-EPMC5706467 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals.

Coppieters Ken T KT Wiberg Anna A Amirian Natalie N Kay Thomas W TW von Herrath Matthias G MG

Diabetes/metabolism research and reviews 20111101 8

<h4>Background</h4>Recent reports have established the notion that many patients with longstanding type 1 diabetes (T1D) possess a remnant population of insulin-producing beta cells. It remains questionable, however, whether these surviving cells can physiologically sense and respond to glucose stimuli.<h4>Methods</h4>Frozen pancreatic sections from non-diabetic donors (n=8), type 2 diabetic patients (n=4), islet autoantibody-positive non-diabetic patients (n=3), type 1 diabetic patients (n=10) ...[more]

PMID: 22069254

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Project description:BackgroundLactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities (e.g., lactose, fructose, galactose), which occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation. A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake. However, it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.AimTo evaluate the blood glucose profile after oral lactulose intake in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.MethodsThis prospective, double-blind, randomized, controlled, single-center trial was conducted at the Clinical Research Center at the Medical University of Graz, Austria, in 24 adult Caucasian mildly constipated, non-insulin-dependent subjects with T2DM. Eligible subjects were randomized and assigned to one of six treatment sequences, each consisting of four treatments stratified by sex using an incomplete block design. Subjects received a single dose of 20 g or 30 g lactulose (crystal and liquid formulation), water as negative control or 30 g glucose as positive control. Capillary blood glucose concentrations were measured over a period of 180 min post dose. The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUCbaseline_c (0-180 min)]. Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose, as well as for liquid lactulose vs crystal lactulose. Safety parameters included GI tolerability, which was assessed at 180 min and 24 h post dose, and adverse events occurring up to 24 h post dose.ResultsIn 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities (≤ 3.0% for crystals and approx. 30% for liquid). The primary endpoint [AUCbaseline_c (0-180 min)] was not significantly different between lactulose and water regardless of lactulose dose and formulation. Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level. A minor increase in maximum blood glucose was observed after the 30 g dose, liquid lactulose, in comparison to water with a mean treatment difference of 0.63 mmol/L (95% confidence intervals: 0.19, 1.07). Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose, respectively (all P < 0.0001). No differences in blood glucose response were observed between the different lactulose formulations. As expected, lactulose increased the number of bowel movements and was generally well tolerated. Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.ConclusionBlood glucose AUCbaseline_c (0-180 min) levels in mildly constipated, non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations.

Project description:AimTo investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 (GLUT2) in obese rat intestinal mucosa.MethodsWe divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group of 16 rats and an obese group of 15. The intervention group was injected with octreotide at 40 μg/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee's index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays.ResultsBody weight, Lee's index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group (605.61 ± 141.00 vs 378.54 ± 111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60 ± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2 ± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ± 3809.60 vs 354.98 ± 57.19, 0.26 ± 0.11 vs 0.07 ± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P < 0.01). Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats (508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60 ±1.38, respectively, all P < 0.05). The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group (269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ±364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ± 0.59, respectively, all P < 0.01).ConclusionHigh fat diet-induced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.

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Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals.

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Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals.

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