scholarly journals Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 933 ◽  
Author(s):  
Silvia Zambrana ◽  
Lena Lundqvist ◽  
Orlando Mamani ◽  
Sergiu-Bogdan Catrina ◽  
Eduardo Gonzales ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Gk Rat ◽  
Gk Rats ◽  
Rat Islets ◽  
Lupinus Mutabilis

Lupinus mutabilis (LM) is a legume part of Bolivian traditional diet that has a nutraceutical property reducing blood glucose levels. The prevalence of type 2 diabetes is increasing worldwide thus; the search for novel anti-diabetic drugs is needed. Based on its traditional use, we evaluated the anti-diabetic effect of LM in the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of type 2 diabetes and in Wistar (W) rats as healthy control. LM seeds hydroethanolic extract, analyzed by gas chromatography-mass spectrometry and high-performance liquid chromatography-high resolution mass spectrometry, is a complex mixture of volatile and non-volatile components. A single oral administration of LM extract (2000 mg/kg b.w.) improved glucose tolerance during the oral glucose tolerance test (OGTT) (30–120 min) in GK and W rats (p < 0.0001). The long-term treatment with LM (1000 mg/kg b.w.), for 21 days, improved the area under the curve (AUC) of glucose during OGTT at day 20, in both GK (p < 0.01) and W rats (p < 0.01). The HbA1c (GK rats, p < 0.05 and W rats, p < 0.0001) and the non-fasting glucose (GK rats, p < 0.05) were also reduced. LM increased both serum insulin levels (2.4-fold in GK rats and 2.5-fold W rats), and the glucose-induced (16.7 mM glucose) insulin release in isolated islets from treated animals (6.7-fold in GK rats, and 6.6-fold in W rats). Moreover, LM (10 mg/mL) stimulated in vitro glucose induced (16.7 mM glucose) insulin release in batch incubated GK and W rat islets (p < 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p < 0.0001), while no significant differences were found in perifused W rat islets. The LM mechanism of action, evaluated using inhibitory compounds of the insulin secretion pathway, showed that LM-dependent insulin secretion was reduced 42% by diazoxide (p < 0.001), 70% by nifedipine (p < 0.001), 86.7% by H89 (p < 0.0001), 70.8% by calphostine-C (p < 0.0001) and 93% by pertussis toxin (p < 0.0001). A similar effect was observed in W rats islets. Our findings provide evidence that LM has an anti-diabetic effect through stimulation of insulin release. The effect is-dependent on L-type calcium channel, protein kinase A and C systems, and G protein-coupled exocytosis and is partially mediated by K-ATP channels.

scholarly journals The possible mechanisms by which phanoside stimulates insulin secretion from rat islets

2007 ◽  
Vol 192 (2) ◽  
pp. 389-394 ◽  
Author(s):  
Nguyen Khanh Hoa ◽  
Åke Norberg ◽  
Rannar Sillard ◽  
Dao Van Phan ◽  
Nguyen Duy Thuan ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cells ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Pertussis Toxin ◽  
Insulin Response ◽  
Gk Rat ◽  
Isolated Pancreatic Islets ◽  
Gk Rats ◽  
Rat Islets

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3.3 and 16.7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 μM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3.3 mM glucose with 150 μM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 μM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide (P<0.01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose (P<0.01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 μM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.

scholarly journals The HND mouse, a nonobese model of type 2 diabetes mellitus with impaired insulin secretion

2005 ◽  
Vol 153 (6) ◽  
pp. 971-979 ◽  
Author(s):  
Fumihiko Horio ◽  
Shin Teradaira ◽  
Tsunehiko Imamura ◽  
Rea Victoria P Anunciado ◽  
Misato Kobayashi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Insulin Release ◽  
Neural Control ◽  
Serum Insulin ◽  
The Philippines

Objectives: This study aimed to develop a novel type 2 diabetes model designated the HND (Horio–Niki diabetic) mouse, by transferring diabetogenic genes from wild castaneus mice (Mus musculus castaneus) captured in the Philippines into laboratory mice (C57BL/6J:B6). Methods: Offspring from the cross between a wild male and a B6 female were backcrossed to the sire. One male backcross which exhibited fasting hyperglycemia was crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed, and mice with impaired glucose tolerance were selected and bred from the F2 generation. Characterization of the phenotype of HND mice and insulin release from their islets was evaluated with F12 generation males. Results: The male HND mice were lean, and spontaneously exhibited impaired glucose tolerance at a high incidence rate at 6 weeks of age. Their serum insulin levels in response to intraperitoneal glucose were markedly attenuated. However, glucose-induced insulin release from isolated HND islets was not affected. Notably, inhibition of glucose-induced insulin release by epinephrine was more pronounced in HND islets than in B6 islets. Moreover, in vivo treatment of HND mice with the α2-adrenergic receptor agonist clonidine resulted in marked hypoinsulinemic hyperglycemia. Conclusions: We suggest the HND mouse may be a distinctive and useful model for type 2 diabetes with impaired neural control of insulin secretion.

Association of plasma acylcarnitines with insulin sensitivity, insulin secretion, and prediabetes in a biracial cohort

2021 ◽  
pp. 153537022110094
Author(s):  
Ibiye Owei ◽  
Nkiru Umekwe ◽  
Frankie Stentz ◽  
Jim Wan ◽  
Sam Dagogo-Jack
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Intravenous Glucose Tolerance Test ◽  
Cross Sectional ◽  
Parental History ◽  
Intravenous Glucose

The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.

scholarly journals Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

2022 ◽  
Author(s):  
Marta Garaulet ◽  
Jesus Lopez-Minguez ◽  
Hassan S Dashti ◽  
Céline Vetter ◽  
Antonio Miguel Hernández-Martínez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Elevated Concentration ◽  
Endogenous Melatonin

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P<sub>int</sub></i><sub> </sub>AUCgluc=0.009, <i>P<sub>int</sub></i><sub> </sub>CIR=0.022, <i>P<sub>int </sub></i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

scholarly journals Dual Mechanism for Type-2 Diabetes Resolution after Roux-en-Y Gastric Bypass

2009 ◽  
Vol 75 (6) ◽  
pp. 498-503 ◽  
Author(s):  
Edward Lin ◽  
S. Scott Davis ◽  
Jahnavi Srinivasan ◽  
John F. Sweeney ◽  
Thomas R. Ziegler ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Peripheral Insulin Resistance

Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose-insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.

Repaglinide treatment amplifies first-phase insulin secretion and high-frequency pulsatile insulin release in Type 2 diabetes

2005 ◽  
Vol 22 (10) ◽  
pp. 1408-1413 ◽  
Author(s):  
M. Hollingdal ◽  
J. Sturis ◽  
M.-A. Gall ◽  
P. Damsbo ◽  
S. Pincus ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Release ◽  
High Frequency ◽  
First Phase Insulin Secretion

Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys18]-substituted analogue

2008 ◽  
Vol 389 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Yasser H.A. Abdel-Wahab ◽  
Gavin J. Power ◽  
Ming T. Ng ◽  
Peter R. Flatt ◽  
J. Michael Conlon
Keyword(s):  
Type 2 Diabetes ◽  
Antimicrobial Activity ◽  
Insulin Secretion ◽  
Insulin Release ◽  
Frog Skin ◽  
Β Cell ◽  
Helical Peptide ◽  
Pseudis Paradoxa ◽  
External Calcium

Abstract Pseudin-2 is a cationic α-helical peptide that was first isolated from the skin of the paradoxical frog Pseudis paradoxa on the basis of its antimicrobial activity. We have investigated the insulin-releasing properties and cytotoxicity of the peptide, together with selected analogues with increased cationicity and hydrophobicity. At concentrations in the range 10-9–10-6 m, pseudin-2, and its [Lys18], [Phe8], and [d-Lys3,d-Lys10,d-Lys14] derivatives, stimulated insulin release from the BRIN-BD11 clonal β-cell line without increasing release of lactate dehydrogenase. The [Lys18] analogue was the most potent (46% increase in insulin release at 10-9 m) and the most effective (215% increase in insulin release at 10-6 m). The more cationic [Lys3,Lys10,Lys14] and [Lys3,Lys10,Lys14,Lys21] analogues lacked insulinotropic action and the more hydrophobic [Phe16] analogue was cytotoxic at concentrations ≥10-7 m. Pseudin-2 and [Lys18]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys18]-pseudin-2 (10-8 m) stimulated insulin release in the presence of diazoxide and verapamil. Our results demonstrate that pseudin-2 stimulates insulin secretion from BRIN-BD11 cells by a mechanism involving Ca2+-independent pathways and identify [Lys18]-pseudin-2 as a peptide that may have potential for development as a therapeutically valuable insulinotropic agent for the treatment of type 2 diabetes.

Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Glucose Effectiveness ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

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