Insulin Secretion and Glucose Tolerance after Islet Transplantation in Rats with Noninsulin-Dependent Diabetes Induced by Neonatal Streptozotocin

1997 ◽  
Vol 6 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Maria-Angeles Tormo ◽  
Trinidad Leon-Quinto ◽  
Catherine Saulnier ◽  
Danielle Bailbe ◽  
Patricia Serradas ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Β Cells ◽  
Basal Plasma

The present study was designed to identify in a model of noninsulin-dependent diabetes induced by neonatal streptozotocin (n0-STZ), the long-term consequences of an islet graft upon 1) glucose handling of the recipient and, 2) glucose response of the residual β cells in the recipient pancreas. We have examined, 4 and 8 wk after islet implantation under the kidney capsule of syngeneic diabetic n0-STZ rats, their tolerance to glucose administered in vivo, together with their insulin release in response to glucose in vivo (oral glucose tolerance test) as well as in vitro (perfused pancreas). The results in the islet-grafted n0-STZ rats, were compared to those obtained in nongrafted nondiabetic rats and nongrafted n0-STZ rats. Our study shows that transplanting a limited number (900) of adult islets under the kidney capsule reverses to normal, many parameters of the noninsulin-dependent diabetic state in the n0-STZ rat model: these include body weight, basal plasma glucose in both the nonfasted and postabsorptive states, and basal plasma insulin in the postabsorptive state. Furthermore, tolerance to oral glucose administration was greatly improved in the transplanted rats and it was correlated with restoration of a manifest glucose-induced insulin secretion in vivo as evaluated (ΔI) during an oral glucose tolerance test. Our data clearly show that the insulin response to glucose from the endogenous pancreas of n0-STZ diabetic rat was not really improved by long-term (8 wk) basal normoglycemia. More precisely, we were able to detect a slight but significant improvement of the early phase of insulin release in vitro in response to glucose; however, the overall insulin response remained 15 times lower than the normal one with no reapparance of the late phase of insulin release. After cessation of glucose stimulation in vivo, off-response of insulin, which is also a landmark of the impaired insulin release by the β cells of n0-STZ rats, was still detectable in the perfused pancreas of the transplanted n0-STZ rats. Finally, because the reactivity to glucose of the endogenous residual β cells was not regained, the insulin released in vivo during the oral glucose test in the graft-bearing n0-STZ rats can be attributed mainly to functioning of the grafted islets population. Copyright © 1997 Elsevier Science Inc.

scholarly journals 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties

1999 ◽  
Vol 277 (4) ◽  
pp. E617-E623 ◽  
Author(s):  
Christophe Broca ◽  
René Gross ◽  
Pierre Petit ◽  
Yves Sauvaire ◽  
Michèle Manteghetti ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Insulin Dependent ◽  
Glucose Tolerance Tests ◽  
Insulin Dependent Diabetic ◽  
Single Intravenous Administration

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 μM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

Reproductive fluids, added to the culture media, contribute to minimizing phenotypical differences between in vitro-derived and artificial insemination-derived piglets

2022 ◽  
pp. 1-13
Author(s):  
Evelyne París-Oller ◽  
Cristina Soriano-Úbeda ◽  
Ramsés Belda-Pérez ◽  
Lucía Sarriás-Gil ◽  
Jordana S. Lopes ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Culture Media ◽  
Growth Parameters ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Long Term Effects ◽  
Hematological Indices ◽  
Reproductive Techniques

Abstract The addition of reproductive fluids (RF) to the culture media has shown benefits in different embryonic traits but its long-term effects on the offspring phenotype are still unknown. We aimed to describe such effects in pigs. Blood samples and growth parameters were collected from piglets derived from in vitro-produced embryos (IVP) with or without RF added in the culture media versus those artificially inseminated (AI), from day 0 to month 6 of life. An oral glucose tolerance test was performed on day 45 of life. We show here the first comparative data of the growth of animals produced through different assisted reproductive techniques, demonstrating differences between groups. Overall, there was a tendency to have a larger size at birth and faster growth in animals derived from in vitro fertilization and embryo culture versus AI, although this trend was diminished by the addition of RFs to the culture media. Similarly, small differences in hematological indices and glucose tolerance between animals derived from AI and those derived from IVP, with a sex-dependent effect, tended to fade in the presence of RF. The addition of RF to the culture media could contribute to minimizing the phenotypical differences between the in vitro-derived and AI offspring, particularly in males.

The Relation Between Glucose Tolerance and Insulin Binding to Circulating Monocytes in Obese Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (4) ◽  
pp. 633-637
Author(s):  
Kaichi Kida ◽  
Noriyoshi Watanabe ◽  
Yoshiki Fujisawa ◽  
Yoshinori Goto ◽  
Hiroshi Matsuda
Keyword(s):  
Glucose Tolerance ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Tolerance Test ◽  
Quantitative Relation ◽  
Immunoreactive Insulin ◽  
Oral Glucose ◽  
Obese Children

The quantitative relation between insulin binding to circulating monocytes in vitro and glucose tolerance in obese children in vivo is reported. Sixty-one obese children and 11 healthy control children participated in this study. The oral glucose tolerance test (OGTT) was performed by giving them glucose (1.75 gm/kg of body weight), orally in the morning, and the binding of 125I-labeled insulin to circulating monocytes in vitro was measured prior to OGTT. The glucose tolerance expressed by ΣBS (milligrams/100 ml), the sum of the plasma glucose (blood sugar [BS]) values at OGTT, was significantly correlated with the degree of overweight (r = .316, P < .01) and more highly with ΣIRI (microunits per milliliter), the sum of immunoreactive insulin (IRI) values at OGTT (r = .512, P < .001). Insulin binding to monocytes in vitro (picograms/106 cells) was inversely correlated with the degree of overweight (r = -. 687, P < .001). Furthermore, ΣBS was inversely correlated significantly with insulin binding to monocytes in vitro (r = -.435, P < .002). These data suggest that the decrease of insulin receptors might be one cause for the impairment of the glucose tolerance associated with obesity in children.

Glucagon-like peptide-1(7-36)-amide confers glucose sensitivity to previously glucose-incompetent beta-cells in diabetic rats: in vivo and in vitro studies

1997 ◽  
Vol 155 (2) ◽  
pp. 369-376 ◽  
Author(s):  
N Dachicourt ◽  
P Serradas ◽  
D Bailbe ◽  
M Kergoat ◽  
L Doare ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Beta Cells ◽  
Insulin Release ◽  
Insulin Response ◽  
Diabetic Rats ◽  
Insulin Response To Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The effects of glucagon-like peptide-1(7-36)-amide (GLP-1) on cAMP content and insulin release were studied in islets isolated from diabetic rats (n0-STZ model) which exhibited impaired glucose-induced insulin release. We first examined the possibility of re-activating the insulin response to glucose in the beta-cells of the diabetic rats using GLP-1 in vitro. In static incubation experiments, GLP-1 amplified cAMP accumulation (by 170%) and glucose-induced insulin release (by 140%) in the diabetic islets to the same extent as in control islets. Using a perifusion procedure, GLP-1 amplified the insulin response to 16.7 mM glucose by diabetic islets and generated a clear biphasic pattern of insulin release. The incremental insulin response to glucose in the presence of GLP-1, although lower than corresponding control values (1.56 +/- 0.37 and 4.53 +/- 0.60 pg/min per ng islet DNA in diabetic and control islets respectively), became similar to that of control islets exposed to 16.7 mM glucose alone (1.09 +/- 0.15 pg/min per ng islet DNA). Since in vitro GLP-1 was found to exert positive effects on the glucose competence of the residual beta-cells in the n0-STZ model. we investigated the therapeutic effect of in vivo GLP-1 administration on glucose tolerance and glucose-induced insulin release by n0-STZ rats. An infusion of GLP-1 (10 ng/min per kg; i.v.) in n0-STZ rats enhanced significantly (P < 0.01) basal plasma insulin levels, and, when combined with an i.v. glucose tolerance and insulin secretion test, it was found to improve (P < 0.05) glucose tolerance and the insulinogenic index, as compared with the respective values of these parameters before GLP-1 treatment.

Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity

1985 ◽  
Vol 59 (1) ◽  
pp. 154-159 ◽  
Author(s):  
J. L. Ivy ◽  
B. A. Frishberg ◽  
S. W. Farrell ◽  
W. J. Miller ◽  
W. M. Sherman
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Muscle Glycogen ◽  
Insulin Response ◽  
Tolerance Test ◽  
Exhaustive Exercise ◽  
Oral Glucose ◽  
Mixed Diet ◽  
Exercise Induced

The effects of an exercise-induced muscle glycogen reduction and an elevated muscle glycogen concentration on glucose tolerance and the insulin response to an oral glucose tolerance test (GTT) were examined. GTTs were administered to seven male subjects after 3 days on a mixed diet (C), after exhaustive exercise and 1 day on a high-fat protein diet (L-FP), after exhaustive exercise and 1 day on a mixed diet (L-M), and after exhaustive exercise and 3 days on a high-carbohydrate diet (H-CHO). The L-M treatment resulted in a significant reduction in muscle glycogen (C, 79.6 +/- 4.2 mmol/kg wet wt vs. L-M, 53.9 +/- 1.2 mmol/kg wet wt) and a 31.7% reduction in the insulin-glucose (IG) index, a measure of insulin sensitivity in vivo. Muscle glycogen was also significantly reduced by the L-FP treatment (49.1 +/- 2.4 mmol/kg wet wt), but there was no change in the IG index. Preventing a decrease in the IG index during the L-FP treatment may have been a result of elevated free fatty acids (67%) and ketones (552%) prior to the GTT. Muscle glycogen was significantly increased by the H-CHO treatment (124.8 +/- 11.1 mmol/kg wet wt); however, the IG index was not different from that of the C treatment. The results suggest that an exercise-induced reduction in muscle glycogen can improve insulin sensitivity in vivo but that this effect is diet dependent.

scholarly journals Suppression of Peroxisome Proliferator-Activated Receptor γ-Coactivator-1α Normalizes the Glucolipotoxicity-Induced Decreased BETA2/NeuroD Gene Transcription and Improved Glucose Tolerance in Diabetic Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4074-4083 ◽  
Author(s):  
Ji-Won Kim ◽  
Young-Hye You ◽  
Dong-Sik Ham ◽  
Jae-Hyoung Cho ◽  
Seung-Hyun Ko ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Receptor Site ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Β Cells ◽  
Β Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Dysfunction

Abstract Peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α) is significantly elevated in the islets of animal models of diabetes. However, the molecular mechanism has not been clarified. We investigated whether the suppression of PGC-1α expression protects against β-cell dysfunction in vivo and determined the mechanism of action of PGC-1α in β-cells. The studies were performed in glucolipotixicity-induced primary rat islets and INS-1 cells. In vitro and in vivo approaches using adenoviruses were used to evaluate the role of PGC-1α in glucolipotoxicity-associated β-cell dysfunction. The expression of PGC-1α in cultured β-cells increased gradually with glucolipotoxicity. The overexpression of PGC-1α also suppressed the expression of the insulin and β-cell E-box transcription factor (BETA2/NeuroD) genes, which was reversed by PGC-1α small interfering RNA (siRNA). BETA2/NeuroD, p300-enhanced BETA2/NeuroD, and insulin transcriptional activities were significantly suppressed by Ad-PGC-1α but were rescued by Ad-siPGC-1α. PGC-1α binding at the glucocorticoid receptor site on the BETA2/NeuroD promoter increased in the presence of PGC-1α. Ad-siPGC-1α injection through the celiac arteries of 90% pancreatectomized diabetic rats improved their glucose tolerance and maintained their fasting insulin levels. The suppression of PGC-1α expression protects the glucolipotoxicity-induced β-cell dysfunction in vivo and in vitro. A better understanding of the functions of molecules such as PGC-1α, which play key roles in intracellular fuel regulation, could herald a new era of the treatment of patients with type 2 diabetes mellitus by providing protection from glucolipotoxicity, which is an important cause of the development and progression of the disease.

scholarly journals Studies of insulin resistance in patients with clinical and subclinical hypothyroidism

2009 ◽  
Vol 160 (5) ◽  
pp. 785-790 ◽  
Author(s):  
Eirini Maratou ◽  
Dimitrios J Hadjidakis ◽  
Anastasios Kollias ◽  
Katerina Tsegka ◽  
Melpomeni Peppa ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
Subclinical Hypothyroidism ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Model Assessment ◽  
Increased Risk

ObjectiveAlthough clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO).Design and methodsTo investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO.ResultsAll three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97±0.22) and SHO (1.99±0.13) versus EU (1.27±0.16, P<0.05), while Matsuda index was decreased in HO (3.89±0.36) and SHO (4.26±0.48) versus EU (7.76±0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 μU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215±19 mean fluorescence intensity, MFI) and SHO (218±24 MFI) versus EU (270±25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481±30 MFI) and SHO (462±19 MFI) were decreased versus EU (571±15 MFI, P=0.04 and 0.004 respectively).ConclusionsIn patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.

scholarly journals Chronic peptide-based GIP receptor inhibition exhibits modest glucose metabolic changes in mice when administered either alone or combined with GLP-1 agonism

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249239
Author(s):  
Jason A. West ◽  
Anastasia Tsakmaki ◽  
Soumitra S. Ghosh ◽  
David G. Parkes ◽  
Rikke V. Grønlund ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Fasting Blood Glucose ◽  
Chronic Administration ◽  
Dual Therapy ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Beneficial Effects ◽  
Gut Hormone ◽  
Gip Receptor

Combinatorial gut hormone therapy is one of the more promising strategies for identifying improved treatments for metabolic disease. Many approaches combine the established benefits of glucagon-like peptide-1 (GLP-1) agonism with one or more additional molecules with the aim of improving metabolic outcomes. Recent attention has been drawn to the glucose-dependent insulinotropic polypeptide (GIP) system due to compelling pre-clinical evidence describing the metabolic benefits of antagonising the GIP receptor (GIPR). We rationalised that benefit might be accrued from combining GIPR antagonism with GLP-1 agonism. Two GIPR peptide antagonists, GIPA-1 (mouse GIP(3–30)NH2) and GIPA-2 (NαAc-K10[γEγE-C16]-Arg18-hGIP(5–42)), were pharmacologically characterised and both exhibited potent antagonist properties. Acute in vivo administration of GIPA-1 during an oral glucose tolerance test (OGTT) had negligible effects on glucose tolerance and insulin in lean mice. In contrast, GIPA-2 impaired glucose tolerance and attenuated circulating insulin levels. A mouse model of diet-induced obesity (DIO) was used to investigate the potential metabolic benefits of chronic dosing of each antagonist, alone or in combination with liraglutide. Chronic administration studies showed expected effects of liraglutide, lowering food intake, body weight, fasting blood glucose and plasma insulin concentrations while improving glucose sensitivity, whereas delivery of either GIPR antagonist alone had negligible effects on these parameters. Interestingly, chronic dual therapy augmented insulin sensitizing effects and lowered plasma triglycerides and free-fatty acids, with more notable effects observed with GIPA-1 compared to GIPA-2. Thus, the co-administration of both a GIPR antagonist with a GLP1 agonist uncovers interesting beneficial effects on measures of insulin sensitivity, circulating lipids and certain adipose stores that seem influenced by the degree or nature of GIP receptor antagonism.

scholarly journals Pharmacological potential of methanol extract of Anacardium occidentale stem bark on alloxan-induced diabetic rats

2018 ◽  
Vol 5 (7) ◽  
pp. 2440-2454
Author(s):  
D. A. Omoboyowa ◽  
F. O. Afolabi ◽  
T. C. Aribigbola
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Methanol Extract ◽  
Stem Bark ◽  
Tolerance Test ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cells

Background: The anti-hyperglycemic potential of methanol stem bark extract of Anacardium occidentale (MSBEAO) was investigated using an alloxan-induced diabetic rat model. Alloxan administration induces the generation of free radicals which can affect antioxidant status resulting in the disruption of the β-cells of the pancreas. Therefore, this study examines the antioxidant potential of the plant extract and the ameliorating effect on the pancreas of alloxan-induced diabetic rats. Methods: Diabetes was induced by intraperitoneal injection of 150 mg/kg body weight of alloxan monohydrate. MSBEAO, at a concentration of 100 or 200 mg/kg b.w. was orally administered to alloxan-induced diabetic rats and normal rats. The hypoglycemic effect, oral glucose tolerance test, and biochemical assay of alloxan-induced diabetic rats were assayed using standard procedures. Results: Preliminary phytochemical screening of the extract revealed the presence of alkaloids, tannins, saponins, terpenoids, carbohydrates, and phenols at moderate concentrations. The lethality dose (LD50) of the plant extract was found to be equal to or less than 5000 mg/kg b.w. The hypoglycemic effect of the extract on the non-diabetic rats revealed a significant (p<0.05) decrease in the blood glucose concentration of animals administered with 1 g/kg b.w. of the extract, compared to normal control rats administered with normal saline. In the oral glucose tolerance test, the methanol extract exerted the highest response, similar to glibenclamide after 15 and 30 minutes of administration, compared to the control rats. The methanol extract yielded the highest blood glucose lowering effects after 9 days of treatment (p<0.05), compared to diabetic rats administered with normal saline and 0.3 mg/kg b.w. of glibenclamide. Administration of the extract at 200 mg/kg b.w. showed improved pancreas architecture and regeneration of the β-cells, compared with the pancreas of animals in the other groups. Conclusion: The results of this study suggest that MSBEAO is a potentially effective agent for the management of diabetes which might result from the antioxidant-generating capacity of the stem bark.

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