Serum Immunoreactive Insulin Levels Research Articles

Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients

AimsThe protein myostatin is a member of the transforming growth factor β superfamily. This is mainly expressed in skeletal muscle and negatively regulates skeletal muscle growth. The present study aimed to elucidate the associations among circulating myostatin level, skeletal muscle mass, and metabolic profiles in Japanese obese patients. MethodsJapanese obese outpatients (n = 74) were enrolled. We measured clinical parameters, quantified serum myostatin levels, and examined their associations in a cross-sectional manner. ResultsBoth total skeletal muscle mass and serum myostatin level were higher in males than in females. Among 74 patients, serum myostatin level was positively correlated with skeletal muscle mass and serum immunoreactive insulin (IRI) level [correlation coefficient (r) = 0.294, P = 0.011; r = 0.262, P = 0.024, respectively]. Furthermore, multivariate linear regression analysis revealed that serum myostatin level was positively correlated with IRI after adjusting for gender and skeletal muscle mass (β-coefficient = 0.230, P = 0.029, R2 = 0.236). ConclusionsIn obese patients, serum myostatin level was elevated in conjunction with an increase in IRI level independent of skeletal muscle mass. This may imply possible novel pathological implications of serum myostatin in muscle mass and metabolism in obese patients with hyperinsulinemia.

Peripheral arterial endothelial dysfunction of neurodegenerative diseases

This study evaluates endothelial functions of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and spinocerebellar ataxia (SCA).The reactive hyperemia index (RHI) of peripheral arterial tonometry and serological data were compared between age- and gender-matched normal controls (n=302) and five disease groups (ALS; n=75, PD; n=180, PSP; n=30, MSA; n=35, SCA; n=53). Correlation analyses were performed in ALS with functional rating scale-revised (FRS-R), and in PD with the Hehn-Yahr scale (H-Y) and a heart to mediastinum ratio using 123I-MIBG scintigraphy (MIBG).The RHI of ALS and PD, but not of PSP, MSA or SCA, were significantly lower than normal controls (p<0.01). ALS showed a negative correlation of RHI with serum triglycerides (TG) and immunoreactive insulin (IRI) levels, but not with disease severity (FRS-R) or rates of disease progression (∆FRS-R). On the other hand, PD showed a negative correlation of RHI with a progressive disease severity (H-Y) and a positive correlation of RHI with early/delayed MIBG scintigraphy, but not with serological data.The present study demonstrated significant declines of peripheral arterial endothelial functions in ALS and PD. The RHI of ALS was more correlated with disease duration and serum parameters while the RHI of PD was more correlated with disease severity and MIBG, suggesting different mechanisms of endothelial dysfunction.

Immunological hypoglycemia associated with insulin antibodies induced by exogenous insulin in 11 Chinese patients with diabetes.

Aims. To investigate the characteristics of immunological hypoglycemia associated with insulin antibodies (IAbs) induced by exogenous insulin in Chinese patients with diabetes. Methods. The clinical data of patients with immunological hypoglycemia due to IAbs were retrospectively analyzed by screening patients with diabetes discharged from West China Hospital from 2007 to 2013. Results. A total of 11 patients (eight men and three women) were identified. Insulin-C-peptide separation was found in all patients via insulin and C-peptide release test. Previous insulin use was ceased after admission and was switched to oral hypoglycemic agents (OHAs) (8/11), lifestyle modification only (2/11), or regular human insulin (1/11). Hypoglycemia was ameliorated after a median of 20 days (interquartile range [IQR], 11–40), while IAbs turned negative after a median of 17 months (IQR, 4–19), and serum immunoreactive insulin (IRI) levels dropped substantially after a median of 22 months (IQR, 9–32) in these cases. Conclusions. In insulin-treated patients with unexpected and refractory hypoglycemia even after insulin therapy was gradually reduced or even withdrawn, IAbs induced by exogenous insulin should be considered, and insulin withdrawal might be promptly needed. The course of immunological hypoglycemia was benign and self-limited.

Repeated Hypoglycemia Caused by the Overproduction of Anti-insulin Antibodies and Isolated ACTH Deficiency in a Type 2 Diabetic Patient Receiving Insulin Therapy

A 46-year-old man with untreated type 2 diabetes visited our hospital. His plasma glucose and HbA1c levels were 429 mg/dL and 11.5%, respectively. He had no renal dysfunction. Insulin therapy (18 units aspart and 22 units biphasic insulin aspart 30/70) was initiated, and the HbA1c level improved (5.7–6.4%). One year later, he started experiencing frequent hypoglycemic attacks, which persisted despite significantly reducing his insulin dosage (total 9 units). Fasting plasma glucose, serum immunoreactive insulin (IRI), C-peptide, and HbA1c levels were 75 mg/dL, 420 μU/mL (reference, 1.7–10.4), 1.2 ng/mL (reference, 0.6–1.8), and 5.4%, respectively. His anti-insulin immunoglobulin G antibody (IA) titer (125I-insulin binding rate) was 95.5% (reference, 0–7.0); free and total IRI levels were 11.0 and >240 μU/mL, respectively. After insulin cessation, …

Insulin Autoimmune Syndrome in a Health Supplement User: The Effectiveness of Cornstarch Therapy for Treating Hypoglycemia

A 70-year-old woman with no history of diabetes was admitted to the hospital for the management of hypoglycemia. Her fasting plasma glucose level was 54 mg/dL with an extremely high serum immunoreactive insulin level (1210 μU/mL). She had high titers of anti-insulin antibodies and exhibited the DRB1*0406 genotype for HLA-DR4, leading to a diagnosis of insulin autoimmune syndrome. She had been taking several health preparations for approximately 10 years; however, all were thiol group-free. Due to frequent episodes of nocturnal hypoglycemia, the health preparations were discontinued and the patient was treated with cornstarch. This protocol successfully ameliorated the hypoglycemic episodes and normalized the patient's laboratory and serological test results.

Relationship between proinsulin and beta cell function in different states of glucose tolerance

To measure proinsulin concentrations in different states of glucose tolerance and examine the relationship between proinsulin and beta cell function. Serum true insulin (TI), proinsulin (PI), immunoreactive insulin (IRI), C peptide (CP) and blood glucose (BG) levels were measured in the fasting state and during an oral glucose tolerance test (OGTT) in 32 individuals with normal glucose tolerance (NGT), 42 individuals with impaired glucose tolerance (IGT), and 54 individuals with newly diagnosed type 2 diabetes mellitus. All participants were also subdivided into nonobese [body mass index (BMI) <25 kg/m2] and obese (BMI ≥25 kg/m2) subgroups. The levels of TI, PI, IRI and CP were higher in obese patients compared with the corresponding NGT subgroup, whereas there was no difference in PI/TI. The levels of IRI, PI and PI/TI were higher in nonobese patients with type 2 diabetes mellitus than in the corresponding NGT subgroup. The levels of PI and TI increased in obese patients with NGT and IGT, whereas PI/TI did not change. In contrast, PI increased but TI did not in subjects with newly diagnosed diabetes mellitus, which led to an increase in PI/TI, and a decrease in beta cell function. Therefore, PI and the PI/TI ratio could offer markers for beta cell dysfunction in DM.

Predictive values of serum insulin kinetics for reversion of impaired glucose tolerance to normal glucose tolerance and the effects of voglibose treatment: a retrospective post hoc analysis of a Japanese phase III study

In a phase III study, voglibose was shown to reduce the risk of development of type 2 diabetes mellitus (T2DM) by 40.5 % in Japanese individuals with impaired glucose tolerance (IGT), and appeared to promote reversion of IGT to normal glucose tolerance (NGT). In a retrospective, post hoc analysis, data from this study, plus follow-up findings from subjects who achieved NGT during the study and who were off-treatment, were analyzed to investigate serum insulin kinetic parameters which might be predictors of IGT reversion to NGT, and maintenance of NGT once achieved. The effects of voglibose on serum insulin kinetics in individuals with IGT were also assessed. Subjects with IGT (n = 1778) were randomized to receive voglibose (0.6 mg/day) or placebo for a mean of 48.1 weeks. During treatment, 1053 subjects achieved NGT, 569 continued to have IGT, and 156 developed T2DM. Analysis of baseline characteristics in each outcome group showed that subjects with higher 30-min serum immunoreactive insulin (IRI) levels in a 75 g oral glucose tolerance test (OGTT) or higher insulinogenic indexes at baseline were more likely to achieve NGT, whether they received voglibose or placebo. Among subjects who achieved NGT, the mean increase in OGTT 30-min IRI level from baseline to endpoint was significantly greater after treatment with voglibose than with placebo. Individuals who had higher OGTT 30-min IRI levels when achieving NGT seemed more likely to sustain this state. Thus, insulin secretion kinetics appeared to predict reversion of IGT to NGT and maintenance of NGT once achieved.

Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: A case report and a review of the literature

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of oral hypoglycemic agents for the management of diabetes that elevate the plasma concentration of active glucagon-like peptide-1 via inhibition of DPP-4. They effectively lower not only glycosylated hemoglobin levels, but also fasting and postprandial plasma glucose levels. Patients with diabetes occasionally consume an overdose of oral hypoglycemic agents in suicide attempts: the prevalence of depression is high in patients with diabetes, and depression is a strong risk factor for suicide. We encountered an 86-year-old woman with type 2 diabetes and depression, who was transferred to the emergency room 4h after ingestion of 1,700 mg of the DPP-4 inhibitor sitagliptin (1,700 mg is 17 times greater than the approved maximum dose). Upon arrival, she was fully conscious, plasma glucose was 124 mg/dL, and serum immunoreactive insulin level was 5.81 µU/mL. Thereafter, the plasma concentration of sitagliptin rose to 3,793 nM, which is 4.5 times higher than the value found under regular treatment with the maximum dose. The patient did not suffer from hypoglycemia, suggesting that a single oral overdose of sitagliptin is unlikely to cause hypoglycemia. A literature review of oral anti-diabetic agents revealed that overdose of biguanides is occasionally fatal when immediate intensive care is not provided. In summary, sitagliptin is a good treatment option for diabetic elderly patients or patients with psychiatric disorders who are suicidal and do not require insulin.

Reduction in Intrasubject Variability in the Pharmacokinetic Response to Insulin After Subcutaneous Co-Administration with Recombinant Human Hyaluronidase in Healthy Volunteers

This study was designed to test the hypothesis that co-administration of recombinant human hyaluronidase (rHuPH20) with regular insulin or insulin lispro will reduce intrasubject variability in pharmacokinetic end points compared with lispro alone. Healthy adult volunteers (18-55 years old) were enrolled in this phase 1, randomized, double-blind, crossover study. Subjects were administered two injections, each on a separate occasion, of three treatments during six euglycemic clamps. Treatments were 0.15 U/kg insulin lispro, 0.15 U/kg insulin lispro with 5 μg/mL rHuPH20, and 0.15 IU/kg regular insulin with 5 μg/mL rHuPH20. Insulin formulations were administered at a concentration of 40 U/mL. Serum immunoreactive insulin levels, blood glucose concentration, and glucose infusion rate determinations were made at baseline and for approximately 8 h after study drug administration. Intrasubject variability was assessed using a general linear mixed model with a fixed effect for treatment using a compound symmetric covariance matrix. Co-injection of rHuPH20 with lispro significantly reduced intrasubject root mean square differences in time to peak serum insulin, time to early 50% peak serum insulin (t(50%)), and time to late t(50%) levels compared with lispro alone. Also, the intrasubject coefficient of variation for percentage of total area under the plasma concentration-versus-time curve for early time intervals compared with lispro alone was reduced. Intrasubject variability for regular insulin with rHuPH20 for most pharmacokinetic parameters was similar to the variability of lispro alone, although variability in early exposure was significantly reduced. Co-administration of rHuPH20 with lispro significantly reduced the variability of insulin pharmacokinetics relative to insulin lispro alone.

Glucose-Responsive Insulinoma in a Patient with Postprandial Hypoglycemia in the Morning

We report the case of an obese 79-year-old woman who experienced postprandial hypoglycemia in the morning. The serum immunoreactive insulin (IRI) and C-peptide levels responded in parallel with her serum glucose level during a 75-g oral glucose tolerance test. A prolonged fast test lowered her serum glucose level to 30 mg/dL, but serum IRI was not fully suppressed. Abdominal computed tomography revealed a tumor in the uncinate process of the pancreas. The tumor was histologically diagnosed as benign insulinoma after surgery. Therefore, glucose-responsive insulinoma as well as reactive hypoglycemia should be considered in patients who exhibit postprandial hypoglycemia.

Insulin Metabolism in Hypothalamic Obesity

Serum C-peptide and Immunoreactive Insulin (IRI) level was measured during per os glucose tolerance test as well as fasting specific insulin binding percentage and capacity of erythrocytes in hypothalamic obesity and in obese children due to hypercalorization, and was compared with ideal-weight controls. Integral values of curves (sigma) and sigma C-peptide/sigma IRI ratios were calculated. In 4 cases fasting C-peptide content was substantially increased as compared to the other groups. The data suggest that hyperinsulinism in diencephalic obesity is primary. The ratio of the two peptides was normal or increased: insulin binding % of erythrocytes corresponded to that of the control group, which explains in these cases normal or favourable glucose metabolism. It is thought that in obese children high fasting C-peptide levels with an adequate clinical picture can indicate the functional examination of the hypothalamic-pituitary system. Sigma C-peptide/sigma IRI ratio differing from normal indirectly shows the changes of receptor function.

Serum bile acid along with plasma incretins and serum high–molecular weight adiponectin levels are increased after bariatric surgery

Bariatric surgery has been shown to improve glucose tolerance, although the mechanism has not been fully elucidated. Animal studies have suggested important roles of bile acid (BA) as a regulator of energy homeostasis and glucose metabolism. However, little is known about its role in humans. We investigated the longitudinal changes of BA, incretins, and adipokines after significant weight reduction in 34 Japanese adults with morbid obesity who underwent laparoscopic bariatric surgery. In subjects who underwent malabsorptive or restrictive surgery, body mass index had markedly decreased from 43.0 ± 6.5 (SD) to 37.8 ± 5.7 kg/m 2 and from 45.3 ± 11.2 to 41.5 ± 10.5 kg/m 2, respectively, at 1 month after surgery. Glycated hemoglobin decreased from 6.1% ± 1.5% to 5.2% ± 0.4% and from 6.2% ± 1.3% to 5.4% ± 0.7%, and total BA level increased from 3.1 ± 3.5 to 7.2 ± 5.3 μmol/L and from 3.2 ± 2.6 to 9.4 ± 10.0 μmol/L, respectively. At baseline, serum concentration of primary BA was positively correlated with plasma gastric inhibitory polypeptide level ( r = 0.548, P = .001); and change in primary BA level was positively correlated with changes in plasma gastric inhibitory polypeptide ( r = 0.626, P = .001) and serum immunoreactive insulin level ( r = 0.592, P = .002) at 1 month after surgery. Furthermore, plasma glucagon-like peptide–1 and serum high–molecular weight adiponectin levels increased in both surgeries. These hormonal changes might explain the mechanism(s) of improved glucose tolerance after bariatric surgery in morbidly obese subjects.

Insulinoma with Six Islet Cell Tumors Associated with Severe Hypoglycemia

A 43-year-old woman was admitted to hospital due to loss of consciousness. Her fasting plasma glucose and serum immunoreactive insulin levels were 14 mg/dL and 5 microU/mL, respectively. She needed continuous glucose infusion to avoid hypoglycemia. A dynamic abdominal CT scan revealed two hypervascular tumors in the pancreas. A pancreatectomy was performed and her blood glucose level was normalized. The pathological examination revealed six insulinomas but we could not find either parathyroid tumors or obvious pituitary tumor, which denied the possibility of multiple endocrine neoplasia type I. However, long-term follow-up will be necessary for monitoring the development of other tumors.

Effect of procainization of ventromedial nucleus of hypothalamus on the feeding behavior of rats.

Bilateral lesions in the Ventromedial nucleus of hypothalamus (VMH) cause hyperphagia and a preference for high lipid, high carbohydrate diet. Reversible lesion by procaine microinfusion produces a decrease in serum glucose and immunoreactive insulin levels. In the present study the effect of procaine microinfusion on feeding behavior and taste preference was observed. 5 h and 24 h food intake, water intake and weekly body weight of the rats was measured. Three bottle preference test was used to study the diet preferences. The 24 h food intake was found to be significantly more on 1st, 2nd and 3rd day (41 ± 6.03, 38.83 ± 6.17 and 33.66 ± 5.88 g/day, respectively) of procaine injection. There was also a significant increase in food intake at 0.25 h (4.166 ± 2.04 g) and 1 h (5 ± 0 g) as compared to saline group (0 ± 0 g at 0.25 h and 0.83 ± 2.04 g at 1 h). Post procaine water intake and body weight for seven days was not statistically significantly when compared to pre-lesion values. In the three bottles preference test, after procaine microinfusion there was a significantly increased preference for 20% sucrose and 0.15% saccharin than quinine and citric acid. The results suggest that bilateral procainization of VMH produces a transient increase in food intake and enhance preference for sweet tasting substances.

Recurrent Hypoglycemia in a Hemodialysis Patient Related to Propoxyphene Treatment

There are various etiologies for hypoglycemia in patients with chronic renal failure, and its pathogenesis is complex. Concomitant use of medications is the most common cause. We report a rare case of an 82-year-old woman with type 2 diabetes mellitus in end-stage renal disease undergoing maintenance hemodialysis, who experienced recurrent symptomatic hypoglycemia during treatment with propoxyphene for pain relief. Hypoglycemia occurred simultaneously with elevated levels of serum immunoreactive insulin and C-peptide. After discontinuing propoxyphene, hypoglycemia mitigated and the level of insulin returned to normal range. Our case reminds us that propoxyphene-induced hypoglycemia should not be ignored, especially in hemodialysis patients with cold sweats, agitation and depressed consciousness.

Colestimide Lowers Plasma Glucose Levels and Increases Plasma Glucagon-like Peptide-1 (7-36) Levels in Patients with Type 2 Diabetes Mellitus Complicated by Hypercholesterolemia

Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia. To examine the mechanism by which colestimide decreases plasma glucose levels in the above patients. A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared. Preprandial plasma glucose levels (baseline: 132 +/- 33 mg/dL vs. completion: 118 +/- 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 +/- 49 mg/dL vs. completion: 166 +/- 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 +/- 56 mg/dL vs. completion: 178 +/- 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels. The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on Hyperglycemia in Streptozotocin-Induced Diabetic Rats

The present study investigated the effects of Hachimi-jio-gan (HJ) on diabetic hyperglycemia in streptozotocin (STZ)-induced diabetic rats. After STZ administration, rats had free access to pellets containing 1% HJ extract powder for four weeks. HJ markedly suppressed hyperglycemia in STZ-induced diabetic rats at three and four weeks after the start of administration. There were also significant increases in serum and pancreatic immunoreactive insulin levels in STZ and HJ co-administering rats. However, in the present study, the number of beta cells in the pancreatic Langerhans' islets did not increase. Next, in order to investigate the action mechanism besides the glycemic control action of insulin, the expression of glucose transporter 2 (GLUT2) protein, which is involved in glucose uptake and release in the liver, was investigated. GLUT2 protein expression was increased by STZ administration but was normalized after four weeks of HJ administration. Therefore, irrespective of the structural changes in pancreatic beta-cells due to STZ, HJ increased insulin production and secretion by the pancreas and significantly suppressed GLUT2 synthesis in the liver. Amylase secretion from the pancreas was measured to assess pancreatic secretion. Amylase activity was decreased by STZ but was increased by HJ. Therefore, the effects of HJ on STZ-induced hyperglycemia in rats could be summarized as follows: besides increasing insulin synthesis and release, HJ normalizes GLUT2 protein expression in the liver to suppress hyperglycemia. Hence, the results of the present study suggest for the first time that HJ affects not only the production and secretion of insulin, but also the release of glucose from the liver.

Medical Treatment of Benign Insulinoma Using Octreotide LAR: A Case Report

In some patients with insulinoma, surgery is not possible due to either difficulties in detecting the tumor or advanced age. These patients need medical treatment for hypoglycemia. We report a case of benign insulinoma using the long-acting octreotide formulation, octreotide long-acting repeatable (octreotide LAR), as a medical therapy. A 67-year-old woman was referred to our hospital for examinations of hypoglycemia. A blood sample taken during a hypoglycemic episode revealed low plasma glucose concentration, hyperinsulinemia and a high C-peptide level. An abdominal CT scan demonstrated a hypervascular tumor in the body of pancreas. She was diagnosed with insulinoma. As the patient refused surgical resection of the pancreas tumor, we started to use the somatostatin analogue, octreotide, for treatment of hypoglycemia. After the treatment her plasma glucose levels were elevated and serum immunoreactive insulin (IRI) levels were decreased. For long-term treatment, we changed the treatment from daily subcutaneous injection of octreotide to monthly intramuscular administration of octreotide LAR. This treatment was also effective and hypoglycemic attacks disappeared. Both plasma glucose levels and serum IRI levels were improved. Our case demonstrated that octreotide LAR was useful for long-term medical treatment of insulinoma.

Effect of cerebrocrast, a new long‐acting compound on blood glucose and insulin levels in rats when administered before and after STZ‐induced diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control. The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.

Effects of Gatifloxacin on Serum Glucose Concentration in Normal and Diabetic Rats

To clarify the mechanisms of gatifloxacin (GFLX)-induced hypoglycemia and hyperglycemia, the effect of GFLX on serum glucose levels was investigated in normal and diabetic rats. Rats received an intravenous injection of GFLX and their arterial blood was sampled periodically. Diabetic rats were produced by the intraperitoneal injection of streptozotocin and nicotinamide. In normal rats, the serum glucose concentration was decreased by GFLX at 25 and 50 mg/kg, while it was elevated 0.25 h after the injection of 100 mg/kg of GFLX. Serum immunoreactive insulin (IRI) levels increased as the dose of GFLX increased. The serum epinephrine concentration rose rapidly after the injection of GFLX at 50 and 100 mg/kg. In diabetic rats, the serum glucose concentration was actually increased by GFLX at 50 mg/kg. The baseline concentration of IRI was lower and the degree of the elevation caused by GFLX was smaller in diabetic rats. Both diabetic and control rats showed an increase in the serum epinephrine concentration after the injection of 50 mg/kg of GFLX. In conclusion, GFLX-induced secretion of insulin and epinephrine would contribute to the abnormalities in glucose homeostasis. The response of serum glucose to GFLX may differ between diabetic and normal rats due to the alteration of insulin secretion.