The Mechanism of Action of Guar Gum in Improving Glucose Tolerance in Man

1. Experiments were carried out in human volunteers to investigate the mechanism by which guar gum improves glucose tolerance. 2. Guar reduced both plasma glucose and insulin responses to an oral glucose load, and delayed gastric emptying. However, there was no correlation between changes in individual blood glucose responses and changes in gastric emptying rates induced by guar. 3. With a steady-state perfusion technique, glucose absorption was found to be significantly reduced during perfusion of the jejunum with solutions containing guar, but returned to control values during subsequent guar-free perfusions. 4. Preperfusing the intestine with guar did not affect electrical measurements of unstirred layer thickness in the human jejunum in vivo.. 5. Experiments in vitro established that glucose diffusion out of a guar/glucose mixture was delayed under conditions of constant stirring. 6. We conclude that guar improves glucose tolerance predominantly by reducing glucose absorption in the small intestine. It probably does this by inhibiting the effects of intestinal motility on fluid convection.

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The effect of ispaghula (Fybogel and Metamucil) and guar gum on glucose tolerance in man

British Journal Of Nutrition ◽

10.1079/bjn19840043 ◽

1984 ◽

Vol 51 (3) ◽

pp. 371-378 ◽

Cited By ~ 55

Author(s):

H. A. Jarjis ◽

N. A. Blackburn ◽

J. S. Redfern ◽

N. W. Read

Keyword(s):

Gastric Emptying ◽

Glucose Tolerance ◽

Plasma Glucose ◽

Plasma Insulin ◽

Guar Gum ◽

Normal Subjects ◽

Oral Glucose ◽

Diabetic Patients ◽

Glucose Plasma ◽

Insulin Responses

1. The effects of incorporating Fybogel (3·5 and 7 g doses), Metamucil (7 g) or guar gum (2·5 and 14·5 g doses) in a drink containing 50 g glucose on plasma glucose, plasma insulin and gastric emptying were studied in thirty-eight normal volunteers. In addition, the effects of Fybogel (7 g) on glucose tolerance, plasma insulin and gastric emptying were measured in fourteen non-insulin-dependent diabetics.2. Both doses of guar gum significantly lowered plasma glucose and plasma insulin responses to the oral glucose load in normal subjects, although 14·5 g guar gum did not delay the half-time for gastric emptying.3. Neither Fybogel nor Metamucil had significant effects on plasma glucose responses in normal subjects. In addition, Fybogel (at either dose) had no significant effects on plasma insulin levels, or on gastric emptying in normal subjects or on plasma glucose and insulin responses in diabetic patients.4. The viscosity of ispaghula solutions (Fybogel) was lower than that of guar gum solutions.

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Antihyperglycemic Effect of Lavandula pedunculata: In Vivo, In Vitro and Ex Vivo Approaches

Pharmaceutics ◽

10.3390/pharmaceutics13122019 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2019

Author(s):

Salima Boutahiri ◽

Mohamed Bouhrim ◽

Chayma Abidi ◽

Hamza Mechchate ◽

Ali S. Alqahtani ◽

...

Keyword(s):

Glucose Tolerance ◽

Aqueous Extract ◽

Digestive Enzymes ◽

Ex Vivo ◽

Glucose Absorption ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Antihyperglycemic Effect

Lavandula pedunculata (Mill.) Cav. (LP) is one of lavender species traditionally used in Morocco to prevent or cure diabetes, alone or in the form of polyherbal preparations (PHP). Therefore, the primary objective of this study was to test the antihyperglycemic effect of the aqueous extract of LP, alone and in combination with Punica granatum L. (PG) and Trigonella foenum-graecum L. (FGK). The secondary objective was to explore some mechanisms of action on the digestive functions. The antihyperglycemic effect of the aqueous extract of LP, alone and in combination with PG and FGK, was studied in vivo using an oral glucose tolerance test (OGTT). In addition, LP extract was tested on the activities of some digestive enzymes (pancreatic α-amylase and intestinal α-glucosidase) in vitro and on the intestinal absorption of glucose ex vivo using a short-circuit current (Isc) technique. Acute and chronic oral administration of LP aqueous extract reduced the peak of the glucose concentration (30 min, p < 0.01) and the area under the curve (AUC, p < 0.01). The effect of LP + PG was at the same amplitude to that of the positive control Metformin (MET). LP aqueous extract inhibited the pancreatic α-amylase with an IC50 almost identical to acarbose (0.44 ± 0.05 mg/mL and 0.36 ± 0.02 mg/mL, respectively), as well as the intestinal α-glucosidase, (IC50 = 131 ± 20 µg/mL) and the intestinal glucose absorption (IC50 = 81.28 ± 4.01 µg/mL) in concentration-dependent manners. LP aqueous extract exhibited potent actions on hyperglycemia, with an inhibition on digestive enzymes and glucose absorption. In addition, the combination with PG and FGK enhanced oral glucose tolerance in rats. These findings back up the traditional use of LP in type 2 diabetes treatment and the effectiveness of the alternative and combinative poly-phytotherapy (ACPP).

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.4.e617 ◽

1999 ◽

Vol 277 (4) ◽

pp. E617-E623 ◽

Cited By ~ 34

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.

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Inhibition of α-Glucosidase, Intestinal Glucose Absorption, and Antidiabetic Properties by Caralluma europaea

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9589472 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Hayat Ouassou ◽

Touda Zahidi ◽

Saliha Bouknana ◽

Mohamed Bouhrim ◽

Hassane Mekhfi ◽

...

Keyword(s):

Ethyl Acetate Fraction ◽

Inhibitory Effect ◽

Tolerance Test ◽

Glucose Absorption ◽

Significant Inhibition ◽

Oral Glucose ◽

Glucosidase Activity ◽

Intestinal Glucose Absorption

Many medicinal plants around the world are used for therapeutic purposes against several diseases, including diabetes mellitus. Due to their composition of natural substances that are effective and do not represent side effects for users, unlike synthetic drugs, in this study, we investigated the inhibitory effect of Caralluma europaea (CE) on α-glucosidase activity in vitro; then the kinetics of the enzyme were studied with increasing concentrations of sucrose in order to determine the inhibition type of the enzyme. In addition, this effect of Caralluma europaea (CE) was confirmed in vivo using rats as an experimental animal model. Among the five fractions of CE, only the ethyl acetate fraction of C. europaea (EACe) induced a significant inhibition of α-glucosidase and its inhibition mode was competitive. The in vivo studies were conducted on mice and rats using glucose and sucrose as a substrate, respectively, to determine the oral glucose tolerance test (OGTT). The results obtained showed that the EACe and the aqueous extract of C. europaea (AECe) have significantly reduced the postprandial hyperglycemia after sucrose and glucose loading in normal and diabetic rats. AECe, also, significantly decreased intestinal glucose absorption, in situ. The results obtained showed that Caralluma europaea has a significant antihyperglycemic activity, which could be due to the inhibition of α-glucosidase activity and enteric absorption of glucose.

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GPR119 Regulates Murine Glucose Homeostasis Through Incretin Receptor-Dependent and Independent Mechanisms

Endocrinology ◽

10.1210/en.2010-1047 ◽

2010 ◽

Vol 152 (2) ◽

pp. 374-383 ◽

Cited By ~ 44

Author(s):

Grace Flock ◽

Dianne Holland ◽

Yutaka Seino ◽

Daniel J. Drucker

Keyword(s):

Insulin Secretion ◽

Gastric Emptying ◽

Glucose Tolerance ◽

Glucose Homeostasis ◽

Peptide Yy ◽

Cell Receptor ◽

Dependent Manner ◽

Glucagon Like Peptide 1

Abstract G protein-coupled receptor 119 (GPR119) was originally identified as a β-cell receptor. However, GPR119 activation also promotes incretin secretion and enhances peptide YY action. We examined whether GPR119-dependent control of glucose homeostasis requires preservation of peptidergic pathways in vivo. Insulin secretion was assessed directly in islets, and glucoregulation was examined in wild-type (WT), single incretin receptor (IR) and dual IR knockout (DIRKO) mice. Experimental endpoints included plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY. Gastric emptying was assessed in WT, Glp1r−/−, DIRKO, Glp2r−/−, and GPR119−/− mice treated with the GPR119 agonist AR231453. AR231453 stimulated insulin secretion from WT and DIRKO islets in a glucose-dependent manner, improved glucose homeostasis, and augmented plasma levels of GLP-1, GIP, and insulin in WT and Gipr−/−mice. In contrast, although AR231453 increased levels of GLP-1, GIP, and insulin, it failed to lower glucose in Glp1r−/− and DIRKO mice. Furthermore, AR231453 did not improve ip glucose tolerance and had no effect on insulin action in WT and DIRKO mice. Acute GPR119 activation with AR231453 inhibited gastric emptying in Glp1r−/−, DIRKO, Glp2r−/−, and in WT mice independent of the Y2 receptor (Y2R); however, AR231453 did not control gastric emptying in GPR119−/− mice. Our findings demonstrate that GPR119 activation directly stimulates insulin secretion from islets in vitro, yet requires intact IR signaling and enteral glucose exposure for optimal control of glucose tolerance in vivo. In contrast, AR231453 inhibits gastric emptying independent of incretin, Y2R, or Glp2 receptors through GPR119-dependent pathways. Hence, GPR119 engages multiple complementary pathways for control of glucose homeostasis.

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

PEDIATRICS ◽

10.1542/peds.70.4.633 ◽

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.

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Peptide-based GIP receptor inhibition exhibits modest metabolic changes in mice when administered either alone or combined with GLP-1 agonism

10.1101/822122 ◽

2019 ◽

Author(s):

Jason A. West ◽

Soumitra S. Ghosh ◽

David G. Parkes ◽

Anastasia Tsakmaki ◽

Rikke V. Grønlund ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Glucose Tolerance ◽

Mouse Model ◽

Metabolic Effects ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Gip Receptor

ABSTRACTObjectiveCombinatorial 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. To this end we investigated the metabolic effects of co-administration of previously reported peptide-based GIPR antagonists with the GLP-1 agonist liraglutide.MethodsTwo GIPR peptide antagonists, GIPA-1 (mouse GIP(3-30)NH2) and GIPA-2 (NαAc-K10[γEγE-C16]-Arg18-hGIP(5–42)), were pharmacologically characterised in vitro in an assay measuring cAMP production in CHO-K1 cells overexpressing the mouse GIPR. These peptides were then characterised in vivo in lean mice for their effect on oral glucose tolerance, as well as their ability to antagonize exogenous GIP action. Finally, a mouse model of diet-induced obesity (DIO) was used to investigate the potential metabolic benefits of chronic dosing of peptide-based GIPR antagonists, alone or in combination with liraglutide.ResultsIn vitro, both GIPR peptides exhibited potent antagonistic properties, with GIPA-2 being the more potent of the two. Acute in vivo administration of GIPA-1 during an oral glucose tolerance test (OGTT) had negligible effects on glucose tolerance and circulated insulin in lean mice. In contrast, GIPA-2 impaired glucose tolerance and attenuated circulating insulin levels, with offsetting effects on glycemia noted with co-administration with exogenous mouse GIP, suggesting true antagonism via GIPA-2 at the GIP receptor. Chronic administration studies in a DIO mouse model showed expected effects of GLP-1 agonism (via 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 with the GIPR antagonists and GLP-1 showed separation from single intervention arms though augmented insulin sensitizing effects (modestly lowering insulin and HOMA-IR) and lowering plasmas triglycerides and free-fatty acids, with more notable effects observed with GIPA-1 compared to GIPA-2.ConclusionWe conclude that, in contrast to the well-documented effects of GLP-1R agonism, systemic administration of peptide-based GIPR antagonists demonstrate minimal benefit on metabolic parameters in DIO mice, exhibiting no major effects on body weight, food intake and glycaemic parameters. However, the co-administration of both a GIPR antagonist together with a GLP1 agonist uncovers interesting synergistic and 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.

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

Cell Transplantation ◽

10.1177/096368979700600106 ◽

1997 ◽

Vol 6 (1) ◽

pp. 23-32 ◽

Cited By ~ 1

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.

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Metabolism of pregnant-lactating rats is adapted to pregnancy rather than to lactation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.4.e766 ◽

1992 ◽

Vol 263 (4) ◽

pp. E766-E771

Author(s):

S. Wijkstra ◽

H. Moes ◽

T. R. Koiter

Keyword(s):

Glucose Tolerance ◽

Fetal Growth ◽

Basal Insulin ◽

Reproductive State ◽

Intravenous Glucose ◽

Glucose Levels ◽

Insulin Responsiveness ◽

Insulin Responses

In pregnant-lactating rats implantation was induced on day 4 of lactation so that, as an exception, lactation coincided with the period of high fetal growth. The already present suckling litters of these animals lagged behind in growth, but the "second" litters were at birth normal in size and weight. Such pregnant-lactating rats were tested in vivo with intravenous glucose loads and compared with cyclic and lactating rats. Glucose tolerance was unaffected by the reproductive state. Pregnant-lactating rats showed, just as during their first pregnancy, low basal glucose levels. Their basal insulin levels and insulin responses, however, were decreased in comparison with the first pregnancy and resembled those of lactating rats. This may be due to an increased insulin turnover, because in vitro insulin responsiveness and insulin content of both "pregnant-lactating" and "pregnant" islets were increased in comparison with "cyclic" and "lactating" islets. It was concluded that the metabolism of pregnant-lactating rats is adapted to the pregnant rather than to the lactational state.

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Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00451.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. E955-E965 ◽

Cited By ~ 22

Author(s):

Serenella Salinari ◽

Alessandro Bertuzzi ◽

Geltrude Mingrone

Keyword(s):

Mathematical Model ◽

Gastric Emptying ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Glucose Absorption ◽

Oral Glucose ◽

Diabetic Patients ◽

Oral Glucose Tolerance

The rate of appearance (Ra) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the Ratime course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the Raprofile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated ( r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose Rameasurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense.

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