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Biomedical subjects

E Araki

Publications and source records attributed to E Araki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex.

The prostanoid-synthesizing enzyme cyclooxygenase-2 (COX-2) is expressed in selected cerebral cortical neurons and is involved in synaptic signaling. We sought to determine whether COX-2 participates in the increase in cerebral blood flow produced by synaptic activity in the somatosensory cortex. In anesthetized mice, the vibrissae were stimulated mechanically, and cerebral blood flow was recorded in the contralateral somatosensory cortex by a laser-Doppler probe. We found that the COX-2 inhibitor NS-398 attenuates the increase in somatosensory cortex blood flow produced by vibrissal stimulation. Furthermore, the flow response was impaired in mice lacking the COX-2 gene, whereas the associated increase in whisker-barrel cortex glucose use was not affected. The increases in cerebral blood flow produced by hypercapnia, acetylcholine, or bradykinin were not attenuated by NS-398, nor did they differ between wild-type and COX-2 null mice. The findings provide evidence for a previously unrecognized role of COX-2 in the mechanisms coupling synaptic activity to neocortical blood flow and provide an insight into one of the functions of constitutive COX-2 in the CNS.

Acetylcholine↗
PubMed2000

Bradykinin enhances insulin receptor tyrosine kinase in 32D cells reconstituted with bradykinin and insulin signaling pathways.

We have previously shown that bradykinin potentiated insulin-induced glucose uptake through GLUT4 translocation in canine adipocytes and skeletal muscles. The aim of this study was to determine the molecular mechanism of bradykinin enhancement of the insulin signal. For this purpose, 32D cells, which express a limited number of insulin receptors and lack endogenous bradykinin B2 receptor (BK2R) or insulin receptor substrate (IRS)-1 were transfected with BK2R cDNA and/or insulin receptor cDNA and/or IRS-1 cDNA, and analyzed. In 32D cells that expressed BK2R and insulin receptor (32D-BKR/IR), bradykinin alone had no effect on the phosphorylation of the insulin receptor, but it enhanced insulin-stimulated tyrosine phosphorylation of the insulin receptor. In 32D cells that expressed BK2R, insulin receptor and IRS-1 (32D-BKR/IR/IRS1), bradykinin also enhanced insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1. An increase in insulin-stimulated phosphorylation of IRS-1 by treatment with bradykinin in 32D-BKR/IR/IRS1 cell was associated with increased binding of 85 kD subunit of phosphatidylinositol 3 (PI 3)-kinase and increased IRS-1 associated PI 3-kinase activity. These effects of bradykinin were not observed in 32D cells which lack the expression of BK2R (32D-IR/IRS1) or insulin receptor (32D-BKR/IRS1). Furthermore, tyrosine phosphatase activity against insulin receptor beta-subunit in plasma membrane fraction of 32D-BKR/IR cells was significantly reduced by bradykinin, suggesting that the effect of bradykinin was in part mediated by inhibition of protein tyrosine phosphatase(s). Our results clearly demonstrated that bradykinin enhanced insulin-stimulated tyrosine kinase activity of the insulin receptor and downstream insulin signal cascade through the BK2R mediated signal pathway.

Animals↗
PubMed2000

Cost-effectiveness of intensive insulin therapy for type 2 diabetes: a 10-year follow-up of the Kumamoto study.

To evaluate the cost and effectiveness of intensive insulin therapy for type 2 diabetes on the prevention of diabetes complications in Japan, we performed economic evaluation based on a randomized controlled trial. A total of 110 patients with type 2 diabetes were randomly assigned into two groups, a multiple insulin injection therapy (MIT) group or a conventional insulin injection therapy (CIT) group, and were followed-up for 10 years. Economic evaluation (cost-consequences analysis) was applied to evaluate both health and economic outcomes. As outcome measures for effectiveness of intensive insulin therapy, the frequency of complications, such as retinopathy, nephropathy, neuropathy, macrovascular event, and diabetes-related death, was used. For estimating costs, a viewpoint of the payer (the National Health Insurance) was adopted. Direct medical costs associated with diabetes care during 10 years were calculated and evaluated. In a base case analysis, all costs were discounted to the present value at an annual rate of 3%. Sensitivity analyses were carried out to assess the robustness of the results to changes in the values of important variables. MIT reduced the relative risk in the progression of retinopathy by 67%, photocoagulation by 77%, progression of nephropathy by 66%, albuminuria by 100% and clinical neuropathy by 64%, relative to CIT. Moreover, MIT prolonged the period in which patients were free of complications, including 2.0 years for progression of retinopathy (P<0.0001), 0.3 years for photocoagulation (P<0.05), 1.5 years for progression of nephropathy (P<0.01) and 2.2 years for clinical neuropathy (P<0.0001). The total cost (discounted at 3%) per patient during the 10-year period for each group was $30310 and 31525, respectively. The reduction of total costs in MIT over CIT was mainly due to reduced costs for management of diabetic complications. Our results show that MIT is more beneficial than CIT in both cost and effectiveness. Therefore, MIT is recommended for the treatment of type 2 diabetic patients who require insulin therapy as early as possible from the perspective of both patients and health policy.

Adult↗
PubMed2000

Involvement of bradykinin in acute exercise-induced increase of glucose uptake and GLUT-4 translocation in skeletal muscle: studies in normal and diabetic humans and rats.

Acute exercise induces glucose uptake in skeletal muscle in vivo, but the molecular mechanism of this phenomenon remains to be identified. In this study, we evaluated the involvement of bradykinin in exercise-induced glucose uptake in humans and rats. In human studies, plasma bradykinin concentrations increased significantly during an ergometer exercise (20 minutes) in 8 healthy normoglycemic subjects and 6 well-controlled type 2 diabetic patients (mean hemoglobin A1c [HbA1c], 6.4% +/- 0.6%), but not in 6 poorly controlled type 2 diabetics (mean HbA1c, 11.6% +/- 2.6%). In rat studies, plasma bradykinin concentrations also significantly increased after 1 hour of swimming in nondiabetic and mildly diabetic (streptozotocin [STZ] 45 mg/kg intravenously [IV]) rats, but not in rats with severe diabetes (STZ 65 mg/kg IV). Glucose influx (maximum velocity [Vmax]) and GLUT-4 translocation in skeletal muscle of nondiabetic rats significantly increased after 1 hour of swimming, but these increases were abrogated by subcutaneous infusion of bradykinin B2 receptor antagonist HOE-140 (400 microg x kg(-1) x d(-1)). Insulin-stimulated tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity in response to insulin injection (20 U/kg IV) in the portal vein were significantly attenuated in exercised rats pretreated with HOE-140 compared with saline-treated exercised rats. Our results suggest that plasma bradykinin concentrations increase in response to acute exercise and this increase is affected by blood glucose status in diabetic patients. Moreover, the exercise-induced increase in bradykinin may be involved in modulating exercise-induced glucose transport through an increase of GLUT-4 translocation, as well as enhancement of the insulin signal pathway, during the postexercise period in skeletal muscle, resulting in a decrease of blood glucose.

Adult↗
PubMed2000

[A case of diabetic polyneuropathy complicated with entrapment neuropathy of the bilateral ulnar nerves due to osteoarthrosis at the elbow].

We report a 61-year-old man with diabetic polyneuropathy and bilateral ulnar nerve palsy due to osteoarthrosis in the elbow. He was diagnosed as having non-insulin dependent diabetes mellitus (DM) at 40 years of age. At 56 years of age, he developed muscle atrophy and weakness predominantly in the distal parts of his upper limbs. A neurological examination showed him to have severe atrophy and weakness in the muscles innervated by the ulnar nerve bilaterally. He also had paresthesia on the distal parts of all four limbs. Superficial and deep sensory deficits were observed in the lower limbs. A motor nerve conduction study showed a marked reduction in the motor conduction velocity as well as in the amplitude of the action potentials of both ulnar nerves. Roentgenograms of the elbow joints and grooves for the ulnar nerve revealed marked osteophyte formation bilaterally. The bilateral ulnar nerve palsy was thus considered to be due to the entrapment of the nerve by the osteophyte. Since several studies have suggested the existence of a relationship between DM and osteoarthropathy, it is important to check for the possible presence of osteoarthrosis in cases of diabetic neuropathy complicated with entrapment neuropathy.

Diabetic Neuropathies↗
PubMed2000

[A case of chronic toluene intoxication presenting stimulus-sensitive segmental spinal myoclonus].

We reported a 48-year-old male who showed stimulus-sensitive spinal myoclonus due to chronic toluene intoxication. He has been exposed to thinner for more than 30 years as a painter, and occasionally experienced an episode of headache, nausea and dizziness because of acute thinner intoxication. He noted tremor of his hands 10 years ago. He also noticed memory disturbance since the end of 1997. Neurological examination revealed postural tremor of his fingers on the bilateral sides and the left arm. In addition, rhythmic myoclonic jerks were induced in the right upper limb muscles by a tendon tap given on the right brachioradialis muscles. Surface EMG revealed repetitive grouping discharges in those two muscles approximately 100 msec after the tendon tap which continued for about 30-50 msec. A long loop reflex (C-reflex) and giant SEPs were not observed in his right upper limb, and EEG showed no spike. Urinary excretion of N-benzoylglycine, which was a metabolite of toluene was increased (1.17 g/l). Therefore, he was diagnosed as a case of chronic toluene intoxication. His myoclonic jerks were considered to be stimulus-sensitive spinal myoclonus, because they were induced segmentally and because cortical hyperexcitability was not seen. This is the first report to describe the occurrence of stimulus-sensitive spinal myoclonus in the case of chronic toluene intoxication.

Chronic Disease↗
PubMed1999

Insulin inhibits glucagon secretion by the activation of PI3-kinase in In-R1-G9 cells.

Intracellular mechanisms through which insulin inhibits glucagon secretion remain to be elucidated in glucagon secreting cells. In this study, we confirmed that, in In-R1-G9 cells, a pancreatic alpha cell line, insulin stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) and activated phosphatidylinositol 3-kinase (PI3-kinase). We further studied, using wortmannin, an inhibitor of PI3-kinase, whether the inhibitory effect of insulin on glucagon secretion was mediated through PI3-kinase pathway in these cells. In static incubation studies, insulin significantly inhibited glucagon secretion at 2, 6 and 12 h, which was completely abolished by pretreatment with wortmannin. In perifusion studies, insulin significantly suppressed glucagon secretion after 10 min, which was also blocked by wortmannin. Insulin also reduced glucagon mRNA at 6 and 12 h but not at 2 h. Wortmannin also abolished insulin-induced reduction of glucagon mRNA. Insulin increased the amount of 85 kDa subunit of PI3-kinase in plasma membrane fraction (PM), with a reciprocal decrease of the kinase in cytosol fraction (CY). Insulin also increased PI3-kinase activity in PM, but not in CY. Our results suggest that insulin suppressed glucagon secretion by inhibiting glucagon release and gene expression. Both actions were mediated by activation of PI3-kinase. Recruitment and activation of PI3-kinase in plasma membrane might be relevant at least in part to insulin-induced inhibition of glucagon release.

Androstadienes↗
PubMed1999

Possible involvement of atypical protein kinase C (PKC) in glucose-sensitive expression of the human insulin gene: DNA-binding activity and transcriptional activity of pancreatic and duodenal homeobox gene-1 (PDX-1) are enhanced via calphostin C-sensitive but phorbol 12-myristate 13-acetate (PMA) and Gö 6976-insensitive pathway.

Pancreatic and duodenal homeobox gene-1 (PDX-1) is a transcription factor which regulates the insulin gene expression. In this study, we tried to elucidate the role of PDX-1 in the glucose-induced transcriptional activation of the human insulin gene promoter in MIN6 cells. Electrophoretic mobility shift assay (EMSA) and chloramphenicol acetyltransferase (CAT) assay demonstrated that both DNA-binding activity and transcriptional activity of PDX-1 were increased with 20 mmol/l glucose more than with 2 mmol/l glucose. The DNA-binding activity of PDX-1 induced by high glucose was blocked by phosphatase treatment, suggesting the involvement of PDX-1 phosphorylation in this event. In an in vitro phosphorylation study, PDX-1 was phosphorylated by protein kinase C (PKC), but not by cAMP dependent protein kinase (PKA) or mitogen-activated protein kinase (MAPK). Furthermore, increased PDX-1 function induced by high glucose was blocked by calphostin C, an inhibitor of all PKC isoforms, but unaffected by phorbol 12-myristate 13-acetate (PMA), an activator of classical and novel PKC, or Gö 6976, an inhibitor of classical and novel PKC, which suggested that the PKC family which activated PDX-1 in MIN6 cells was atypical PKC. Western blot and immunocytochemical studies with anti-PKC zeta antibody confirmed the presence of PKC zeta, one of the isoforms of atypical PKC, in MIN6 cells. Furthermore, PKC zeta activity was significantly increased by glucose stimulation. These results suggest that high glucose increased DNA-binding activity of PDX-1 by activating atypical PKC including PKC zeta, resulting in transcriptional activation of the human insulin gene promoter.

Animals↗
PubMed1999

[A case of motor and sensory polyneuropathy with retinitis pigmentosa and diffuse idiopathic skeletal hyperostosis].

We here report a 53-year-old man who presented with motor and sensory polyneuropathy, retinitis pigmentosa and diffuse idiopathic skeletal hyperostosis (DISH). He had a 15-year history of diabetes mellitus (DM). Visual impairment appeared at 17 years of age. Since age 47, he showed a slowly progressive sensory impairment and muscle weakness of the extremities. On neurological examination, retinitis pigmentosa and severe muscle atrophy, muscle weakness and sensory disturbance of all modalities in the distal portions of all four extremities were observed. Deep tendon reflexes were absent. A plain X-P showed diffuse ossification of the spinal and extraspinal ligaments. The motor nerve conduction velocities were severely reduced and no sensory nerve action potentials were evoked. The CSF examination revealed an increased protein level without pleocytosis. The sural nerve biopsy showed a marked onion bulb formation and a loss of the myelinated nerve fibers, which could not be solely explained by DM. As the phytanic acids levels, beta-lipoprotein, lactate and pyruvate in the sera were within the normal ranges, Refsum disease, Bassen-Kornzweig syndrome and mitochondrial diseases were unlikely in this patient. The presence of demyelinating and axonal polyneuropathy in this patient may have been caused by a common metabolic disturbance which produced both retinitis pigmentosa and DISH.

Diabetes Complications↗
PubMed1999

[Polymyositis and cutaneous vasculitis in a patient with myelodysplastic syndrome].

We report a 60-year-old man with myelodysplastic syndrome (MDS) who developed polymyositis and cutaneous vasculitis. He noticed difficulty in climbing up stairs 4 months before admission. On admission, he showed brownish skin pigmentation in the distal positions of the four extremities. Neurological examination revealed muscle weakness of the neck flexor and proximal muscles of four extremities. Serum myogenic enzymes including creatine kinase increased, and electromyography showed denervation potentials and MUPs were myogenic, which was compatible with polymyositis. Muscle biopsy indicated perivascular mononuclear cell infiltration and muscle fiber necrosis with cytoplasmic bodies and rimmed vacuoles in the muscle fibers. Complete blood cell counts revealed macrocytic normochromic anemia and bone marrow puncture disclosed marked hyperplasia of megakaryocytes, erythroblasts and myeloblasts, suggesting a refractory anemia type of MDS. In addition, skin biopsy showed chronic cutaneous vasculitis. Serum protein electrophoresis and immunoelectrophoresis revealed the presence of IgM gamma type monoclonal gammopathy. With immunosuppressive therapy, serum creatine kinase level was decreased. Since immunological abnormalities and the presence of autoimmune diseases have been reported in patients with MDS, both polymyositis and chronic cutaneous vasculitis in the present patient may be caused by the similar autoimmune mechanisms related to MDS.

Autoimmune Diseases↗
PubMed1999

[A case of progressive hemifacial atrophy with Pourfour de Petit syndrome which was successfully treated by stellate ganglion block].

We herein report a 31-year-old woman with progressive hemifacial atrophy. The atrophy at her left face began about ten years ago. She had been in a traffic accident one year before the onset of her facial atrophy. Neurological examination revealed anisocoria (right < left) and retraction of the left eyelid, which thus suggested the presence of Pourfour de Petit syndrome. The pupillary reaction to both cocaine and tyramine were reduced bilaterally. Thermography of the face showed slightly lower surface temperature on the left side. A facial thermal sweat test was normal. These findings indicated local hyperactivity of the sympathetic nervous system at the Th 1-Th2 levels on the left side. A left stellate ganglion block effectively induced an accumulation of the subcutaneus tissue of her face on the left side. This is a very rare case in which local sympathetic hyperactivity is present and has caused progressive hemifacial atrophy.

Adult↗
PubMed1999

[A case of radiculomyelitis following chickenpox in adulthood].

A 34-year-old woman presented with numbness in both lower limbs and weakness of right lower limb twenty six days after a primary varicella infection (chickenpox) associated with fever and rash. Neurological examination revealed numbness of both lower limbs, more severe on the right side, mild paresis of the right lower limb, particularly in the tibialis anterior muscle, and absent ankle jerk on the right. After admission, hyperalgesia appeared at the thoracic 10-12 levels. The T2-weighted MRI of the spinal cord revealed a high signal intensity lesion at the Th 9 level and gadolinium enhancement was seen in that lesion as well as in the bilateral posterior radicles and the left anterior radix at the Th 9 level. On needle electromyography, fasciculation was found in the right tibialis anterior and gastrocnemius muscles. The temporal dispersion of F-wave was seen in the right peroneal nerve. We diagnosed the patient suffered from radiculomyelitis following the primary varicella infection. The secondary immunological mechanism rather than direct viral invasion is most likely in our patient, because (1) neither VZV DNA, nor anti-VZV antibody was positive in the CSF, and (2) the duration was relatively long between the development of skin rash and that of neurological symptoms.

Adult↗
PubMed1999

[A case of congenital non-progressive cerebellar ataxia with pigmentary retinal degeneration, fiber type disproportion and hypercreatine kinasemia].

We report a 20-year-old female who presented with congenital non-progressive cerebellar ataxia, pigmentary retinal degeneration, fiber type disproportion, hypercreatine kinasemia and mental retardation. No family history of neuromuscular disorders was found. There was consanguinity between the grandfather and grandmother. Pregnancy and delivery were uneventful. Although neck control was obtained at three months old, she could walk at 23 months old. She had a tendency to tumble. Her mentality was retarded. At 12-years-old, she was diagnosed as having pigmentary retinal degeneration. When she visited to our hospital at 20-year-old, she had slight scoliosis. Neurological examination disclosed mental retardation, pigmentary retinal degeneration, gaze evoked nystagmus on horizontal gaze and proximal dominant muscle weakness. Tandem gait was unsteady. Deep tendon reflexes were slightly hyperactive in all four extremities. The serum creatine kinase was elevated to 2346U/l. Muscle biopsy revealed type I. fiber atrophy and predominance. This case is therefore considered to be cogenital non-progressive cerebellar ataxia presenting with fiber type disproportion, pigmentary retinal degeneration and hypercreatine kinasemia.

Adult↗
PubMed1998

Cellular characterization of pituitary adenoma cell line (AtT20 cell) transfected with insulin, glucose transporter type 2 (GLUT2) and glucokinase genes: insulin secretion in response to physiological concentrations of glucose.

We investigated the mechanisms of insulin secretion by transfecting into a pituitary adenoma cell line (AtT20) a combination of genes encoding human insulin (HI), glucose transporter type 2 (GLUT2) and glucokinase (GK), followed by studying the characteristics of these cells. In static incubation, a cell line transfected with insulin gene alone (AtT20HI) secreted mature human insulin but this was not in a glucose-dependent manner. Other cell lines transfected with insulin and GLUT2 genes (AtT20HI-GLUT2-3) or with insulin and GK genes (AtT20HI-GK-1) secreted insulin in response to glucose concentrations of only less than 1 mmol/l. In contrast, cell lines transfected with insulin, GLUT2 and GK genes (AtT20HI-GLUT2-GK-6, AtT20HI-GLUT2-GK-7 and AtT20HI-GLUT2-GK-10) showed a glucose-dependent insulin secretion up to 25 mmol/l glucose. Glucose utilization and oxidation were increased in AtT20HI-GLUT2-GK cell lines but not in AtT20HI, AtT20HI-GLUT2-3 and AtT20HI-GK-1 cells at physiological glucose concentrations, compared with AtT20 cells. Diazoxide, nifedipine and 2-deoxy glucose suppressed (p < 0.05) glucose stimulated insulin secretion in AtT20HI-GLUT2-GK-6 cells. Glibenclamide, KCl or corticotropin releasing factor (CRF) stimulated (p < 0.05) insulin secretion both in AtT20HI and AtT20HI-GLUT2-GK-6 cells. Insulin secretion stimulated by glibenclamide, KCl or CRF was further enhanced by the addition of 25 mmol/l glucose in AtT20HI-GLUT2-GK-6 cells but not in AtT20HI cells. In perifusion experiments, a stepwise increase in glucose concentration from 5 to 25 mmol/l stimulated insulin secretion in AtT20HI-GLUT2-GK cell lines but the response lacked a clear first phase of insulin secretion. Our results suggest that both GLUT2 and glucokinase are necessary for the glucose stimulated insulin secretion in at least rodent cell lines, and that other element(s) are necessary for a biphasic insulin secretion typically observed in beta cells.

Adenoma↗
PubMed1998

Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts.

Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain reaction) amplification showed mRNA specific for bradykinin B2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.

Animals↗
PubMed1998

Creation and characterization of a mitochondrial DNA-depleted pancreatic beta-cell line: impaired insulin secretion induced by glucose, leucine, and sulfonylureas.

It has been proposed that mitochondrial oxidative phosphorylation in pancreatic beta-cells plays an important role in insulin secretion. To examine the impact of mitochondrial dysfunction on insulin secretion, we created a MIN6 cell line that depleted mitochondrial DNA (mtDNA) by treatment with ethidium bromide (EtBr), and studied the response of the cell line to various secretagogues. MIN6 cells cultured with 0.5 microg/ml EtBr for over 2 months (termed MIN6 deltamt cells) revealed a marked (>90%) decrease in mtDNA content and a lack of mRNAs encoded by mtDNA. MIN6 deltamt cells showed the defects of cytochrome c oxidase activity, glucose- and leucine-induced increase in cellular ATP content, and respiratory chain-driven ATP synthesis, suggesting that MIN6 deltamt cells lost oxidative phosphorylation activity due to the selective disruption of the subunits of respiratory chain enzymes encoded by mtDNA. MIN6 deltamt cells also showed a decrease in glucose utilization, suggesting the impairment of the glycolytic pathway as well. After stimulation with glucose and leucine, MIN6 deltamt cells showed no response in insulin secretion or intracellular free Ca2+ concentration ([Ca2+]i). On the other hand, arginine stimulated insulin secretion and an increase in [Ca2+]i in MIN6 deltamt cells as in MIN6 cells. Glibenclamide also stimulated insulin secretion and an increase in [Ca2+]i in both types of cells, but the responses of MIN6 deltamt cells were significantly lower than those of MIN6 cells. These results suggest the importance of ATP production in insulin secretion and an increase in [Ca2+]i, both induced by glucose and leucine. Moreover, mitochondrial function turns out to be not essential but important for the activation of sulfonylurea-induced insulin secretion.

Adenosine Triphosphate↗