Biomedical subjects

M Shichiri

Publications and source records attributed to M Shichiri.

At least 145 records · Page 8Linked to original sources

PubMed1994

Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method. Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients.

OBJECTIVE: To develop a reliable and practical glucose monitoring system by combining a needle-type glucose sensor with a microdialysis sampling technique for long-term subcutaneous tissue glucose measurements. RESEARCH DESIGN AND METHODS: A microdialysis Cuprophan hollow-fiber probe (inner diameter, 0.20 mm; length, 15 mm) was perfused with isotonic saline solution (120 microliters/h) and glucose concentrations in the dialysate were measured by a needle-type glucose sensor extracorporeally. This system was tested both in vitro and in vivo. Subcutaneous tissue glucose concentrations were then monitored continuously in 5 healthy and 8 diabetic volunteers for 7 to 8 days. A hollow-fiber probe was inserted into the abdominal subcutaneous tissue. RESULTS: This monitoring system achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to > 27.8 mM glucose, with a time delay of 6.9 +/- 1.2 min associated with a rise in glucose and 8.8 +/- 1.6 min with a fall in the glucose level (means +/- SE). The overall correlation between subcutaneous tissue (Y) and blood (X) glucose concentration was Y = 1.08X + 0.19 (r = 0.99). The subcutaneous tissue glucose concentration could be monitored precisely for 4 days without any in vivo calibrations and for 7 days by introducing in vivo calibrations. CONCLUSIONS: Glycemic excursions could be monitored precisely in the subcutaneous tissue by this microdialysis sampling method with a needle-type glucose sensor in ambulatory diabetic patients.

Adult↗

PubMed1994

[Characterization and expression of the insulin receptor gene and its promoter].

Insulin initiates diverse biological effects by binding to the insulin receptor. The insulin receptor gene is located on the short arm of chromosome 19 and is more than 130 kb in length and contains 22 exons. Two species of mRNAs encoding insulin receptors that differ 12 amino acids in length exist by alternative splicing of the exon 11. The promoter region of the human insulin receptor gene is extremely GC rich and lacks typical TATA and CAAT boxes but contains multiple potential binding sites of Sp1, which are the characteristics of a "housekeeping" gene. Possible regulation of the expression of the insulin receptor gene by hormones such as insulin and dexamethasone and some transcription factors including Sp1 and C/EBP have been shown at the mRNA and transcription levels.

Animals↗

PubMed1994

[Characterization of the IRS-1 (insulin receptor substrate-1) gene and its promoter].

IRS-1 (insulin receptor substrate-1) is a major substrate of the insulin receptor. Rat and human IRS-1 cDNAs, and human and mouse IRS-1 genes have been cloned so far. They show high homology in nucleic acids and amino acids levels, which indicate the high conservation of IRS-1 across the species. Interestingly, the entire coding region is contained in the 1st exon in the IRS-1 gene. The promoter of the mouse IRS-1 gene lacks TATA and CAAT boxes but contains 9 potential Spl binding sites, indicating that IRS-1 is a "housekeeping" gene. By deletion analysis, two positively and two negatively regulating fragments are identified in the promoter. In cultured adipocytes, insulin and dexamethasone down regulate IRS-1 expression by different mechanisms. Insulin down regulates at the post-translational level by shortening the protein half life, and dexamethasone down regulates at the post-transcriptional level mainly by shortening the mRNA half life.

Animals↗

PubMed1993

Two independent macrophage receptors for acetylated high-density lipoprotein.

We previously demonstrated that acetylated human high-density lipoprotein (acetyl-HDL) was recognized by a scavenger receptor of rat sinusoidal liver cells (Murakami, M., Horiuchi, S., Takata, K. and Morino, Y. (1987) J. Biochem. (Tokyo) 101, 729-741). The present study describes the interaction of acetyl-HDL with rat peritoneal macrophages in vitro. Acetylation of HDL enhanced its cell-association by 2-fold and cellular degradation by > 25-fold. The cell-association of [125I]acetyl-HDL was effectively inhibited by unlabeled acetyl-HDL (> 85%), whereas the inhibition by HDL or acetylated human low-density lipoprotein (acetyl-LDL) was partial (60% and 50%, respectively). However, when both HDL and acetyl-LDL were present, the cell-association of [125I]acetyl-HDL was effectively inhibited by > 80%, a level identical or closely similar to that by acetyl-HDL. The cellular degradation of [125I]acetyl-HDL was effectively suppressed by acetyl-LDL whereas the effect of HDL was much weaker. These findings indicate that acetyl-HDL is endocytosed by both the HDL receptor and the scavenger receptor for acetyl-LDL in which the ligands bound to the latter might be subjected to lysosomal degradation.

Acetylation↗

PubMed1993

Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes.

The effect of angiotensin (ANG) II on the expression of endothelin (ET) receptor subtype (ETA, ETB) mRNA in cultured neonatal rat cardiomyocytes was studied. ANG II (10(-7) M) increased steady-state mRNA levels of ETB receptor, but not ETA receptor, during 6-12 hr incubation, whose effect was dose-dependent (10(-9)-10(-7) M). ANG II receptor type-1 (AT1) antagonist (CV-11974) completely inhibited the ANG II-induced up-regulation of ETB receptor, whereas the inhibitory effect by ANG II receptor type-2 (AT2) antagonist (PD 123319) was incomplete. These results suggest that ANG II up-regulates cardiac ETB receptor, predominantly via AT1 receptor.

Angiotensin II↗

PubMed1993

Noninvasive measurement of blood glucose concentrations by analysing Fourier transform infra-red absorbance spectra through oral mucosa.

Whether Fourier transform infra-red spectroscopy with an attenuated total reflection prism could be applied for noninvasive glucose measurement through oral mucosa was evaluated. As a result, the same absorbance peak at 1033 cm-1 as in glucose aqueous solution was found in the absorbance spectra through mucous membrane. However, these glucose specific peaks were interfered with by the baseline drifts owing to prism attachment and the background spectra from body constituents other than glucose. Therefore, to eliminate these interferences, the calibration curve between the second derivatives of the absorbance peak at 1033 cm-1 and those at 2920 cm-1 was calculated (r = 0.910). By using this calibration curve, the spectral changes due to prism attachment were first eliminated. Secondly, by obtaining the second derivative of the difference between the postprandial absorbance peak and the fasting sample as a characteristic of an individual, high correlations between the corrected second derivatives of absorbance spectra through the mucous membrane of the lip at 1033 cm-1 and the increases in blood glucose concentrations above fasting levels were observed (r = 0.910). In conclusion, it was suggested that Fourier transform infra-red spectroscopy could be useful for noninvasive monitoring of glucose through oral mucosa.

Blood Glucose↗

PubMed1993

Improvement in blunted glucagon response to insulin-induced hypoglycemia by strict glycemic control in diabetics.

To elucidate the mechanism of impaired pancreatic A cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations on hypoglycemia-induced glucagon secretion was studied. Firstly, the effect of plasma insulin concentrations on suppressing A cell was studied in healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. With 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to those with 0.1 U/kg of insulin by glucose infusion with artificial endocrine pancreas. Plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin, demonstrating that not only hypoglycemic stimulus but also plasma insulin concentration were important determinants responsible for glucagon secretion in insulin-induced hypoglycemia. Secondly, effect of strict glycemic control was studied. Short-acting insulin at a dose of 0.1 U/kg was injected in an intravenous bolus form into 12 insulin-dependent (IDDM) and 9 non-insulin-dependent (NIDDM) diabetics before and 1-3 months after strict glycemic control with multiple insulin injections therapy. Before strict glycemic regulations in IDDM, no significant rise in plasma glucagon concentrations was observed during the insulin-induced hypoglycemia. In NIDDM, a rise in plasma glucagon concentrations was observed, though the response was delayed. After strict glycemic regulations, in patients with residual endogenous insulin secretion, the glucagon response to hypoglycemia improved considerably in IDDM and normalized in NIDDM. In IDDM and NIDDM, improvement in glucagon response to hypoglycemia related positively to daily urinary secretion rate of C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Effects of dietary protein restriction on hemodynamics in chronic renal failure.

To elucidate the effect of protein and phosphorus restriction on hemodynamics in chronic renal failure, 14 patients were placed on a low-protein very-low-phosphorus diet (LPVLPD) and observed for metabolic and hemodynamic changes. For three weeks after initiation of the LPVLPD, the patients displayed a positive sodium balance in spite of dietary sodium restriction. During the fourth week, sodium balance decreased and approached zero. Sodium retention was accompanied by a significant decrease in plasma renin activity (P < 0.05) and mean blood pressure (P < 0.01), an increase in body weight (P < 0.05), a slight temporary decrease in hemoglobin (P < 0.05), hematocrit (P < 0.05) and total protein (P < 0.005), a negative nitrogen balance, and an increase in left ventricular ejection fraction (P < 0.01) and peak filling rate (P < 0.05). Serum creatinine concentration and endogenous creatinine clearance did not change during the experiment. These data indicate a role of dietary protein and phosphorus restriction in cardiac and fluid homeostasis in the pathophysiology of chronic renal failure.

Aged↗

PubMed1993

Atrial natriuretic peptide in the pericardial fluid of patients with heart disease.

1. The pericardial fluid of 20 open heart surgery patients with acquired heart disease was analysed for atrial natriuretic peptide by radioimmunoassay. 2. The concentration of atrial natriuretic peptide in the pericardial fluid was significantly higher than in the corresponding plasma (316.8 +/- 50.0 versus 121.7 +/- 29.1 pg/ml; P < 0.01) and was higher in patients with congestive heart failure than in those without heart failure (469.3 +/- 78.6 versus 181.8 +/- 26.7 pg/ml; P < 0.001). Pericardial and plasma atrial natriuretic peptide concentrations showed a significant positive correlation. Pericardial fluid and plasma samples were fractionated using both reverse-phase high-performance liquid chromatography and gel permeation chromatography. Each fraction was assayed for atrial natriuretic peptide by radioimmunoassay, revealing the presence of beta-atrial natriuretic peptide as well as alpha- and gamma-atrial natriuretic peptide. 3. The pericardial fluid concentration of cyclic GMP, the intracellular second messenger for atrial natriuretic peptide, was significantly higher in patients with congestive heart failure than in patients without heart failure.

Adult↗

PubMed1993

Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes.

BACKGROUND: Cardiac hypertrophy is commonly observed in acromegalic patients, in whom serum insulin-like growth factor-I (IGF-I) levels are elevated. In the present study, we examined whether IGF-I induces hypertrophy in cultured neonatal rat cardiomyocytes through its specific receptor and whether IGF binding protein-3 (IGFBP-3), which is a major circulating carrier protein for IGF-I, inhibits IGF-I-induced cardiac hypertrophy in vitro. METHODS AND RESULTS: Because the response of cardiac hypertrophy is characterized by the induction of expression for muscle-specific genes, the effect of IGF-I on steady-state levels of mRNA for myosin light chain-2 (MLC-2) and troponin I and for skeletal and cardiac alpha-actin isoforms was evaluated by Northern blot analysis. IGF-I (10(-7) M) increased mRNA levels for MLC-2 and troponin I as early as 60 minutes with maximum levels by 6 hours, which were maintained for as long as 24 hours. IGF-I (10(-7) M) also increased transcripts for skeletal alpha-actin but not for cardiac alpha-actin. The cell size as evaluated morphometrically was almost doubled after 48-hour treatment with IGF-I. IGF-I induction of protein synthesis was dose dependent (10(-10) to 10(-7) M) with a maximal 2.2-fold increase seen at 10(-8) M. In contrast to the hypertrophic effect of IGF-I, growth hormone affected neither protein synthesis nor expression for muscle-specific genes. Binding study using 125I-IGF-I revealed the presence of specific binding sites for IGF-I in rat cardiomyocytes. IGFBP-3 induced a dose-dependent inhibition of protein synthesis stimulated by IGF-I; IGFBP-3 (10(-7) M) completely inhibited the [3H]leucine uptake stimulated by IGF-I (10(-8) M). IGFBP-3 similarly inhibited the IGF-I-stimulated gene expressions for MLC-2 and troponin I. CONCLUSIONS: These results suggest that IGF-I directly causes cardiac hypertrophy and that its effect can be blocked by IGFBP-3.

Actins↗

PubMed1993

Clinical features of recurrent embolization in acute cardioembolic stroke.

BACKGROUND AND PURPOSE: Recurrent embolization is a serious problem in acute cardioembolic stroke. However, the clinical features and predisposing factors of recurrent embolization have not been fully elucidated. METHODS: Subjects were 227 consecutive patients (128 men and 99 women, aged 68.6 +/- 13.2 years) with acute cardioembolic stroke who did not receive anticoagulant therapy during the first 14 days after stroke onset. We assigned the subjects to two groups according to the occurrence or nonoccurrence of recurrent attacks within 14 days of the stroke onset. We assessed their clinical features, coagulation study results, and underlying heart disease. RESULTS: Recurrent brain or systemic embolization during the first 14 days after onset was noted in 46 patients (20.3%, group A) but not in the other 181 (group B). Recurrent embolization was more frequently noted at an early phase than at a late phase during the initial 14 days. Mortality was higher in group A (19.6%) than in group B (8.8%). The mean plasma level of antithrombin III (77.8 +/- 19.5%) at admission in group A patients was significantly lower than that in group B patients (87.9 +/- 15.5%). After admission, hematocrit decreased in group B patients but slightly increased in group A patients, in whom diuretics were more commonly used. Rheumatic heart disease and prosthetic valves, in addition to the presence of intracardiac thrombi, were seen more commonly in group A patients, whereas atrial fibrillation without organic heart disease and myocardial infarction were more frequent in group B patients. CONCLUSIONS: Low plasma levels of antithrombin III, dehydration, the use of diuretics, and the presence of rheumatic heart disease, prosthetic valves, and intracardiac thrombi seem to be predisposing factors for recurrent embolization. Immediate anticoagulation may be considered in acute cardioembolic stroke patients if such predisposing factors are demonstrated.

Aged↗

PubMed1993

Distribution of atherosclerosis and risk factors in atherothrombotic occlusion.

BACKGROUND AND PURPOSE: The present study was performed to determine the relation between distribution of atherosclerosis and risk factors in Japanese patients with atherothrombotic occlusion. METHODS: We studied 154 patients with atherothrombotic occlusion of the extracranial internal carotid artery (n = 75, ICA group), the horizontal portion of the middle cerebral artery (n = 47, MCA group), and the basilar artery (n = 32, BA group), all of which were confirmed by cerebral angiography. We investigated the distribution of atherosclerosis of the three sites and compared the risk factors for atherosclerosis between the three groups. We used 113 subjects without stroke as the control group. RESULTS: A strong correlation was present between atherosclerosis of the extracranial internal carotid artery and that of the basilar artery. However, only a weak correlation existed between atherosclerosis of the middle cerebral artery and that of the other vessels. Although the prevalence of smoking and hypertension was higher and high density lipoprotein cholesterol levels were lower in the three groups than in the control subjects, no significant differences were found in age, sex, prevalence of smoking and hypertension, serum levels of triglycerides, and high density lipoprotein cholesterol among the three groups. The prevalence of coronary heart disease and diabetes mellitus and the serum levels of hemoglobin A1c, total cholesterol, and low density lipoprotein cholesterol were higher in the ICA and BA groups than in the MCA group. The prevalence of electrocardiographic evidence of left ventricular hypertrophy was higher in the MCA group than in the other groups. CONCLUSIONS: In addition to smoking, hypertension, and low concentration of high density lipoprotein cholesterol, diabetes mellitus and hypercholesterolemia seem to be associated with atherosclerosis of the extracranial internal carotid artery and the basilar artery, and advanced hypertension may play a role in the development of middle cerebral artery occlusion.

Adult↗

PubMed1993

A cell culture model system for genetic analyses of the cell cycle by targeted homologous recombination.

Analysis of how external proliferation signals impinge on the regulation of the cell cycle is ideally performed in cells that are capable of normal physiological withdrawal into the quiescent (G0) phase of the cell cycle as well as resumption of growth following appropriate stimuli. Targeted homologous recombination (gene targeting) provides an important new approach to determine the function of specific genes in these cellular processes. Current gene targeting methodology necessitates the use of immortal and stably diploid cell lines. This report investigates several rodent cell lines, by both genetic and physiological criteria, for use in gene targeting studies of the G0 to G1 transition. All murine cell lines examined were aneuploid. Some rat cell lines were euploid by chromosome number, but three specific genes, c-myc, c-raf-1 and Rb, were not always diploid. Only one cell line, an early-passage subclone of the Rat-1 cell line, was diploid for c-myc, c-raf-1 and Rb. An hprt- derivative of this cell line was isolated (designated TGR-1) and its karyotype was established by G-banding. TGR-1 cells were shown to withdraw into G0 upon serum starvation and to uniformly enter S phase after refeeding. Expression patterns of the c-myc, c-raf-1 and Rb genes and several properties of the gene products were found to be normal. The frequency of targeted homologous recombination of the c-myc and c-raf-1 loci was found to be within values observed with other cell lines. Thus, by both genetic and physiological criteria the TGR-1 cell line is a good model system for the analysis of the roles of c-myc, c-raf-1 and Rb in signal transduction, and will probably prove useful in studies involving other genes.

Animals↗

PubMed1993

Effects of c-myc expression on proliferation, quiescence, and the G0 to G1 transition in nontransformed cells.

The relative contributions of deregulation versus high level expression of the c-myc gene to malignant transformation are not clear. To investigate the effects of subtle perturbations in c-myc expression on normal cellular physiology, we isolated cell lines with one c-myc gene copy disrupted by targeted homologous recombination. The heterozygous cell lines were further modified by introducing a c-myc transgene expressed 4-fold above the normal diploid level. During exponential growth, heterozygous cells expressed c-Myc mRNA at approximately 50% of the level found in diploid cells, resulting in a slower growth rate. The c-myc transgene reversed the growth defect and accelerated growth relative to diploid cells. Serum deprivation of transgene-expressing cells caused a fraction of the culture to undergo apoptosis. After an initial wave of apoptosis, the remainder of the culture successfully entered Go. Transgene mRNA continued to be constitutively expressed in quiescent cells, but c-Myc protein was not detectable. During the G0 to G1 transition, heterozygous cells induced c-myc expression with normal kinetics, but levels throughout the time course were consistently at least 50% lower than those in diploid cells. The reduction in c-myc expression was correlated with a 3-4-h delay in entry into S phase. The presence of the transgene, which was expressed constitutively throughout the G0 to G1 transition, reversed the delay but did not further accelerate entry into S phase. Our results show that even small perturbations in c-myc expression cause changes in the proliferative status of cells and thus argue that the natural regulation patterns of the gene are crucial for the maintenance of normal cellular physiology.

Animals↗

PubMed1992

Cross-linking of apolipoproteins is involved in a loss of the ligand activity of high density lipoprotein upon Cu(2+)-mediated oxidation.

A recent study demonstrated that Cu(2+)-mediated oxidation of high density lipoprotein (HDL) resulted in a loss of the capacity to reduce cholesterol from macrophage foam cells [(1991) Proc. Natl. Acad. Sci. USA 88, 6457-6461]. In the present study we characterized the physicochemical properties of oxidized HDL and correlated them with the ligand activity toward the HDL receptor. Among them, the cross-linking of apolipoproteins and an increase in lipid peroxides were characteristic and closely similar to those of tetranitromethane-treated HDL, an abortive ligand for the HDL receptor. Cellular experiments with murine peritoneal macrophages revealed that both the cellular binding activity of HDL and its capacity to enhance cholesterol efflux from macrophage foam cells were markedly reduced upon oxidation. These results suggest that cross-linking of HDL apolipoproteins is involved in the loss of the ligand activity of oxidized HDL.

Animals↗

PubMed1992

Exposure of rat peritoneal macrophages to acetylated low density lipoprotein results in release of plasma membrane cholesterol. An efficient substrate for esterification by acyl-CoA:cholesterol acyltransferase.

In J774 macrophages and murine macrophages stimulated with acetylated low density lipoprotein (acetyl-LDL), the plasma membrane free cholesterol (FC) became accessible to acyl-CoA:cholesterol acyltransferase (ACAT) as substrate, the result being an accumulation of cholesteryl esters (CE) (Tabas, I., Rosoff, W. J., and Boykow, G. C (1988) J. Biol. Chem. 263, 1266-1272). As the route of delivery of FC to ACAT was not well characterized, we examined this route in the present study. In foam cells derived from rat peritoneal macrophages by preincubation with acetyl-LDL, esterification of the exogenously labeled [3H]FC was low (1.3% of total labeled cholesterol). In contrast, when cells were first labeled with exogenous [3H]FC and then chased with acetyl-LDL, the esterification was more extensive (9.2% of the total labeled cholesterol). During this experiment a significant portion of cellular [3H]FC was released into the medium (up to 33.4% of the total labeled cholesterol). In experiments using a two-compartment chamber in which cells in the lower and upper chambers were separated by filter paper yet the cells in both compartments could communicate without direct contact, [3H]FC released into the medium was biologically active and could serve as an efficient substrate for ACAT. Thus, when acetyl-LDL is not included in culture medium, FC delivery from the macrophage plasma membrane to ACAT is not enhanced, whereas in the presence of acetyl-LDL, plasma membrane FC released and bound to acetyl-LDL may re-enter the cells, possibly through the scavenger receptor. This would provide a significant route for CE synthesis in macrophages.

Animals↗

PubMed1992

Increased production of endothelin-1 in patients with inflammatory arthritides.

OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, but its precise mechanism of action in vivo has remained unknown. METHODS: We measured ET-1 activity by radioimmunoassay, in both plasma and synovial fluid from patients with inflammatory arthritides. RESULTS: ET-1-like immunoreactivity was found in synovial fluid, at levels severalfold higher than those in plasma. Reverse-phase high-performance liquid chromatography showed an elution profile corresponding to actual ET-1. A single class of high-affinity binding sites for ET-1 in cultured synovial cells was also detected. Furthermore, ET-1 induced mild DNA synthesis in synovial cells. CONCLUSION: Taken together, these results indicate that ET-1 might contribute to the synovial proliferation seen in inflammatory arthritides, in an autocrine/paracrine manner.

Adult↗

PubMed1992

Normoglycemia per se but not normoinsulinemia is responsible for suppressing endogenous insulin secretion after oral glucose load in NIDDM.

It is well known that intensive insulin treatment of non-insulin-dependent diabetics (NIDDM) suppresses endogenous insulin secretion and thereafter improves it. To determine whether 'peripheral normo-insulinemia' or 'normoglycemia' established by the treatment is responsible for this suppression, the following five experiments were conducted on 15 well-controlled non-obese NIDDM patients. Experiment 1: a 100 g oral glucose load (OGL) was performed and blood glucose was monitored by an artificial endocrine pancreas (AP). Experiment 2: a 100 g OGL was done and blood glucose was normalized by AP-controlled insulin infusion. Experiments 3 and 4: a 100 g OGL was conducted while 'hyperglycemia' seen in experiment 1 was mimicked by AP-controlled glucose infusion with pre-programmed insulin infusion at the same rates as those in experiment 2 ('normoinsulinemia') or at rates 1.5 times higher than those in experiment 2 ('relative hyperinsulinemia'), respectively. Experiment 5: a 40 g OGL was conducted while AP-controlled insulin and glucose infusions were administered to make the plasma insulin level lower than in experiment 2 ('hypoinsulinemia') and to mimic the normoglycemic profile observed in experiment 2, respectively. In experiments 3 and 4, neither 'normoinsulinemia' nor 'relative hyperinsulinemia' suppressed the increase in plasma C-peptide after a 100 g OGL. In experiment 5, where the plasma insulin level showed a significantly (P less than 0.05) lower level than in experiment 2 and glycemia was normalized, C-peptide did not show a significant rise after OGL. These results indicate that 'normoglycemia' rather than 'normoinsulinemia' attained during exogenous insulin therapy, is responsible for suppressing endogenous insulin secretion against orally administered glucose.

Blood Glucose↗