Rapid quantitative PCR equipment using photothermal conversion of Au nanoshell.

The emergence of infectious diseases worldwide necessitates rapid and precise diagnostics. Using gold nanoshells in the PCR mix, we harnessed their unique photothermal properties in the near-infrared regime to attain efficient heating, reaching ideal photothermal PCR cycle temperature profile. Our photothermal PCR method expedited DNA amplification while retaining its detection sensitivity. Combining photothermal quantitative PCR with real-time fluorometry and non-invasive temperature measurement, we could amplify the target DNA within just 25 min, with a minimum detectable DNA amount of 50 picograms. This innovation in photothermal qPCR, leveraging the photothermal properties of gold nanoshells, will pave the way for immediate point-of-care diagnostics of nucleic acid biomarkers.

Heterogeneity in liver histopathology is associated with GSK-3ß activity and mitochondrial dysfunction in end-stage diabetic rats on differential diets.

While liver histopathology is heterogeneous in diabetes, the underlying mechanisms remain unclear. We investigated whether glycemic variation resulting from differential diets can induce heterogeneity in diabetic liver and the underlying molecular mechanisms. We generated end-stage non-obese diabetic model rats by subtotal-pancreatectomy in male Sprague- Dawley rats and ad libitum diet for 7 weeks (n = 33). The rats were then divided into three groups, and fed a standard- or a low-protein diet (18 or 6 kcal%, respectively), for another 7 weeks: to maintain hyperglycemia, 11 rats were fed ad libitum (18AL group); to achieve euglycemia, 11 were calorierestricted (18R group), and 11 were both calorie- and proteinrestricted with the low-protein diet (6R group). Overnightfasted liver samples were collected after the differential diets together with sham-control (18S group), and histology and molecular changes were compared. Hyperglycemic-18AL showed glycogenic hepatopathy (GH) without steatosis, with the highest GSK-3ß inactivation because of Akt activation during hyperglycemia; mitochondrial function was not impaired, compared to the 18S group. Euglycemic-18R showed neither GH nor steatosis, with intermediate GSK-3ß activation and mitochondrial dysfunction. However, euglycemic-6R showed both GH and steatosis despite the highest GSK-3ß activity and no molecular evidence of increased lipogenesis or decreased ApoB expression, where mitochondrial dysfunction was highest among the groups. In conclusion, heterogeneous liver histopathology developed in end-stage non-obese diabetic rats as the glycemic levels varied with differential diets, in which protein content in the diets as well as glycemic levels differentially influenced GSK-3ß activity and mitochondrial function in insulin-deficient state. [BMB Reports 2020; 53(2): 100-105].

Pyroprotein-Based Electronic Textiles with High Stability.

Thermally reducible pyroprotein-based electronic textiles (e-textiles) are fabricated using graphene oxide and a pyroprotein such as cocoon silk and spider web without any chemical agents. The electrical conductivity of the e-textile is 11.63 S cm-1 , which is maintained even in bending, washing, and temperature variation.

Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities.

Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW) compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R) or 6 kcal% (6R) protein-containing chow or fed ad libitum (19AL). The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S). Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.

Optical field enhancement of nanometer-sized gaps at near-infrared frequencies.

We report near-field and far-field measurements of transmission through nanometer-sized gaps at near-infrared frequencies with varying the gap size from 1 nm to 10 nm. In the far-field measurements, we excluded direct transmission on the metal film surface via interferometric method. Kirchhoff integral formalism was used to relate the far-field intensity to the electric field at the nanogaps. In near-field measurements, field enhancement factors of the nanogaps were quantified by measuring transmission of the nanogaps using near-field scanning optical microscopy. All the measurements produce similar field enhancements of about ten, which we put in the context of comparing with the giant field enhancements in the terahertz regime.

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats.

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

Operation of a wet near-field scanning optical microscope in stable zones by minimizing the resonance change of tuning forks.

A resonant shift and a decrease of resonance quality of a tuning fork attached to a conventional fiber optic probe in the vicinity of liquid is monitored systematically while varying the protrusion length and immersion depth of the probe. Stable zones where the resonance modification as a function of immersion depth is minimized are observed. A wet near-field scanning optical microscope (wet-NSOM) is operated for a sample within water by using such a stable zone.

Epsilon-near-zero meta-lens for high resolution wide-field imaging.

Herein, we will propose a new application possibility of epsilon-near-zero (ENZ) materials: high resolution wide-field imaging. We show that the resolution can be dramatically enhanced by simply inserting a thin epsilon-near-zero (ENZ) material between the sample and substrate. By performing metal half-plane imaging, we experimentally demonstrate that the resolution could be enhanced by about 47% with a 300-nm-thick SiO2 interlayer, an ENZ material at 8-µm-wavelength (1250 cm-1). The physical origin of the resolution enhancement is the strong conversion of diffracted near fields to quasi-zeroth order far fields enabled by the directive emission of ENZ materials.

Improvement of ß-cell function after achievement of optimal glycaemic control via long-term continuous subcutaneous insulin infusion therapy in non-newly diagnosed type 2 diabetic patients with suboptimal glycaemic control.

BACKGROUND: Achieving euglycaemia by continuous subcutaneous insulin infusion (CSII) therapy alone has been shown to restore ß-cell function in patients with newly diagnosed type 2 diabetes. However, the efficacy has not been evaluated in patients with non-newly diagnosed type 2 diabetes and suboptimal glycaemic control. METHODS: Of the 1220 patients with type 2 diabetes who began CSII therapy from March 2000 to March 2007, we retrospectively selected patients using the following inclusion criteria: glycosylated haemoglobin (HbA1c ) ≥ 7.0%, diabetes duration ≥ 1 year before CSII therapy, and duration of CSII therapy ≥ 6 months. We evaluated sequential changes in HbA1c and serum C-peptide levels measured at a 6- to 12-month intervals during CSII therapy. RESULTS: In the 521 subjects included in this study [median diabetes duration 10 years; interquartile range (IQR) 6.0-17.0; CSII therapy ≤ 30 months], median HbA1c decreased from 8.7% (IQR 7.7-10.0) at baseline to 6.3% (IQR 5.9-6.9) after 6 months of CSII therapy (p < 0.0001). During the subsequent 24 months, median HbA1c levels were maintained between 6.3% and 6.5% (p < 0.0001 for all time points vs baseline). At 12 months after CSII therapy, median C-peptide levels began to increase compared with baseline (fasting level 23% increase, p < 0.0001; 2-h postprandial level 26% increase, p = 0.022), and the increase was maintained at 30 months (fasting level 39%; 2-h postprandial level 53%; p < 0.0001 for all vs baseline). CONCLUSIONS: ß-Cell function was significantly improved in patients with non-newly diagnosed and suboptimally controlled type 2 diabetes after achieving and maintaining optimal glycaemic control with long-term CSII therapy alone.

Emission properties of hydrothermal Yb(3+), Er(3+) and Yb(3+), Tm(3+)-codoped Lu2O3 nanorods: upconversion, cathodoluminescence and assessment of waveguide behavior.

Yb(3+) and Ln(3+) (Ln(3+) = Er(3+) or Tm(3+)) codoped Lu(2)O(3) nanorods with cubic Ia3 symmetry have been prepared by low temperature hydrothermal procedures, and their luminescence properties and waveguide behavior analyzed by means of scanning near-field optical microscopy (SNOM). Room temperature upconversion (UC) under excitation at 980 nm and cathodoluminescence (CL) spectra were studied as a function of the Yb(+) concentration in the prepared nanorods. UC spectra revealed the strong development of Er(3+) (4)F(9/2) → (4)I(15/2) (red) and Tm(3+) (1)G(4) → (3)H(6) (blue) bands, which became the pre-eminent and even unique emissions for corresponding nanorods with the higher Yb(3+) concentration. Favored by the presence of large phonons in current nanorods, UC mechanisms that privilege the population of (4)F(9/2) and (1)G(4) emitting levels through phonon-assisted energy transfer and non-radiative relaxations account for these observed UC luminescence features. CL spectra show much more moderate development of the intensity ratio between the Er(3+) (4)F(9/2) → (4)I(15/2) (red) and (2)H(11/2), (4)S(3/2) → (4)I(15/2) (green) emissions with the increase in the Yb(3+) content, while for Yb(3+), Tm(3+)-codoped Lu(2)O(3) nanorods the dominant CL emission is Tm(3+) (1)D(2) → (3)F(4) (deep-blue). Uniform light emission along Yb(3+), Er(3+)-codoped Lu(2)O(3) rods has been observed by using SNOM photoluminescence images; however, the rods seem to be too thin for propagation of light.

Insulin requirement profiles of patients with type 2 diabetes after achieving stabilized glycemic control with short-term continuous subcutaneous insulin infusion.

BACKGROUND: As in type 1 diabetes, continuous subcutaneous insulin infusion (CSII) therapy is emerging as a promising therapeutic option in type 2 diabetes. However, the insulin requirement profiles of patients with type 2 diabetes when treated via CSII with rapid-acting insulin analogs have not been well investigated. METHODS: We examined insulin requirement profiles of type 2 diabetes patients (n = 300; age, 57.9 +/- 11.4 years; hemoglobin A1c [HbA(1c)], 9.1 +/- 2.2%) for 3 days after achieving normoglycemia via 1-2 weeks of CSII therapy. We also analyzed the total daily dose (TDD) of insulin-associated clinical and laboratory parameters at baseline. RESULTS: The mean TDD was 45.1 +/- 24.7 IU/day (range, 4.8-145.8 IU/day). The total daily bolus (TBo) (range 2.8-111.3 IU/day) was 64.1 +/- 12.1% of the TDD. The rates of infusion for day and night in total daily basal dose (TBa) were 0.74 +/- 0.35 and 0.41 +/- 0.32 IU/h, respectively. The dose ratio (in IU/day) was 2.7 : 1.9 : 1.6 : 1.8 : 1 (breakfast, lunch, and dinner bolus and day and night basal, respectively). After adjusting for age, gender, and body mass index, TDD was associated with HbA(1c), fasting and 2-h postprandial plasma glucose, fasting C-peptide, and carbohydrate-to-insulin ratio (P < 0.05). CONCLUSIONS: Initial TDD in type 2 diabetes patients on CSII showed a wide range of distribution with a TBo-to-TBa ratio >2.0 and was associated with parameters indicating glycemic control but not with body weight, suggesting that the currently used protocol in dose determination of insulin, including allocation of half of the TDD to TBa or weight-based determination of initial TDD, may need to be reexamined when treating type 2 diabetes with CSII therapy.

Improvement of cardiovascular risk factors in patients with type 2 diabetes after long-term continuous subcutaneous insulin infusion.

BACKGROUND: The effects of long-term continuous subcutaneous insulin infusion (CSII) on cardiovascular risk factors such as hyperglycaemia, dyslipidaemia, and proinflammatory cytokine levels have not been assessed so far in type 2 diabetes. METHODS: We analysed the levels of HbA(1c), serum lipids, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) at 0, 2, and 30 weeks after CSII in 15 patients with type 2 diabetes (mean age, 53.3+/-10.1 years; disease duration, 9.4+/-5.3 years) without previous history of major cardiovascular events. RESULTS: At week 30, CSII significantly lowered HbA(1c) by 5.0+/-0.9% compared to baseline (7.9+/-1.9%, p<0.001) and improved high-density lipoprotein cholesterol (HDLc; 1.09+/-0.16 at baseline vs 1.25+/-0.15 mmol/L at week 30; p<0.05) and low-density lipoprotein cholesterol (LDLc)/HDLc ratios (2.8+/-1.4 at baseline vs 2.2+/-0.9 at week 30; p<0.05). CSII also decreased the proportion of patients with dyslipidaemia at week 30. At baseline, TNF-alpha and IL-6 levels were up-regulated (2.65+/-4.04 and 2.82+/-1.81 pg/mL, respectively) compared to the normal control (p<0.01 and p<0.05, respectively); however, cytokine levels decreased significantly at week 30 (1.44+/-2.25 and 1.99+/-1.05 pg/mL, respectively; p=NS vs control). CONCLUSIONS: Long-term CSII alone decreased cardiovascular risk factors in poorly controlled type 2 diabetes, suggesting that the synchronization of sufficient insulin peaks with meal ingestion and continuous pulsatile infusion of basal insulin corrects metabolic derangements.

Exercise and dexamethasone oppositely modulate beta-cell function and survival via independent pathways in 90% pancreatectomized rats.

Long-term dexamethasone (DEX) treatment is well known for its ability to increase insulin resistance in liver and adipose tissues leading to hyperinsulinemia. On the other hand, exercise enhances peripheral insulin sensitivity. However, it is not clear whether DEX and/or exercise affect beta-cell mass and function in diabetic rats, and whether their effects can be associated with the modulation of the insulin/IGF-I signaling cascade in pancreatic beta-cells. After an 8-week study, whole body glucose disposal rates in 90% pancreatectomized (Px) and sham-operated male rats decreased with a high dose treatment of DEX (0.1mg DEX/kg body weight/day)(HDEX) treatment, while disposal rates increased with exercise. First-phase insulin secretion was decreased and delayed by DEX via the impairment of the glucose-sensing mechanism in beta-cells, while exercise reversed the impairment of first-phase insulin secretion caused by DEX, suggesting ameliorated beta-cell functions. However, exercise and DEX did not alter second-phase insulin secretion except for the fact that HDEX decreased insulin secretion at 120 min during hyperglycemic clamp in Px rats. Unlike beta-cell functions, DEX and exercise exhibited increased pancreatic beta-cell mass in two different pathways. Only exercise, through increased proliferation and decreased apoptosis, increased beta-cell mass via hyperplasia, which resulted from an enhanced insulin/IGF-I signaling cascade by insulin receptor substrate 2 induction. By contrast, DEX expanded beta-cell mass via hypertrophy and neogenesis from precursor cells, rather than increasing proliferation and decreasing apoptosis. In conclusion, the improvement of beta-cell function and survival via the activation of an insulin/IGF-I signaling cascade due to exercise has a crucial role in preventing the development and progression of type 2 diabetes.

Insulin sensitizing and alpha-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma.

Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.

Effects of okchun-san, a herbal formulation, on blood glucose levels and body weight in a model of Type 2 diabetes.

The effective control of blood glucose is the key to preventing or reversing diabetic complications. In this study, we examined the effects of Okchun-San (OCS), a Korean herbal medicine formula, on the blood glucose levels in diabetic C57BL/KsJ db/db mice. Herbal medicines were prepared from dried herbs by adding Coicis semen (OCS-C) or Oryzae semen (OCS-O). The experimental animals were divided into a control group and three sample groups; the sample groups received OCS-C (200 mg/kg), OCS-O (200 mg/kg), or acarbose (5 mg/kg) orally once a day for 12 days. On days 5 and 12, the fasting blood glucose levels of vehicle-treated db/db mice were significantly higher than day 0, while those of OCS-C, OCS-O, or acarbose-treated mice had not increased compared to the control group (p<0.01). During intraperitoneal glucose tolerance test (IPGTT), OCS-C group showed improved glucose sensitivity compared to the control group. These results suggest that OCS-C can be useful as an anti-diabetic therapy for Type 2 diabetic patients by lowering the blood glucose level.

Tramadol enhances hepatic insulin sensitivity via enhancing insulin signaling cascade in the cerebral cortex and hypothalamus of 90% pancreatectomized rats.

Clinical observation found that tramadol, mu opioid receptor (MOR) agonist and serotonin (5-HT) reuptake inhibitor, has a hypoglycemic effect in type 2 diabetes patients. The mechanism of its hypoglycemic effect has not been fully defined. This study showed that tramadol activated a neuronal insulin signaling cascade by increasing the induction of insulin receptor substrate-2 expression in primary cultured neuronal cells while this activation was suppressed by naloxone (MOR inhibitor) and dexamethasone (non-specific inhibitor of MOR and 5-HT receptor, DEX). Glucose utilization of the cerebral cortex and hypothalamus was enhanced by a 4-week-tramadol administration in 90% pancreatectomized rats, in vivo, as assessed by measurement of glucokinase expression and glycogen deposition via activating insulin signaling cascade such as neuronal cells in vitro. This improvement was almost completely suppressed by naloxone as well as DEX. Tramadol decreased fasted serum glucose levels, favored an increase in the glucose infusion rate and reduced endogeneous hepatic glucose production after 4 weeks of treatment. However, tramadol did not modulate hepatic glucose output directly, as exhibited by liver perfusion, suggesting tramadol altered hepatic glucose utilization through the effect of organs other than the liver, possibly the central nervous system. The data suggest that tramadol ameliorates peripheral glucose metabolism through central activation of MOR, and that central and peripheral glucose metabolism are therefore likely to be interrelated.

Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma.

Our preliminary study demonstrated that 70% ethanol Cortidis Rhizoma extracts (CR) had a hypoglycemic action in diabetic animal models. We determined whether CR fractions acted as anti-diabetic agent, and a subsequent investigation of the action mechanism of the major compound, berberine ([C(20)H(18)NO(4)](+)), was carried out in vitro. The 20, 40 and 60% methanol fractions from the XAD-4 column contained the most insulin sensitizing activities in 3T3-L1 adipocytes. The common major peak in these fractions was berberine. Treatment with 50 microM berberine plus differentiation inducers significantly reduced triglyceride accumulation by decreased differentiation of 3T3-L1 fibroblasts to adipocytes and triglyceride synthesis. Significant insulin sensitizing activity was observed in 3T3-L1 adipocytes which were given 50 microM berberine plus 0.2 nM insulin to reach a glucose uptake level increased by 10 nM of insulin alone. This was associated with increased glucose transporter-4 translocation into the plasma membrane via enhancing insulin signaling pathways and the insulin receptor substrate-1-phosphoinositide 3 Kinase-Akt. Berberine also increased glucose-stimulated insulin secretion and proliferation in Min6 cells via an enhanced insulin/insulin-like growth factor-1 signaling cascade. Data suggested that berberine can act as an effective insulin sensitizing and insulinotropic agent. Therefore, berberine can be used as anti-diabetic agent for obese diabetic patients.

Estrogen and exercise may enhance beta-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats.

The prevalence and progression of type 2 diabetes have increased remarkably in postmenopausal women. Although estrogen replacement and exercise have been studied for their effect in modulating insulin sensitivity in the case of insufficient estrogen states, their effects on beta-cell function and mass have not been studied. Ovariectomized (OVX) female rats with 90% pancreatectomy were given a 30% fat diet for 8 wk with a corresponding administration of 17beta-estradiol (30 microg/kg body weight) and/or regular exercise. Amelioration of insulin resistance by estrogen replacement or exercise was closely related to body weight reduction. Insulin secretion in first and second phases was lower in OVX during hyperglycemic clamp, which was improved by estrogen replacement and exercise but not by weight reduction induced by restricted diets. Both estrogen replacement and exercise overcame reduced pancreatic beta-cell mass in OVX rats via increased proliferation and decreased apoptosis of beta-cells, but they did not exhibit an additive effect. However, restricted diets did not stimulate beta-cell proliferation. Increased beta-cell proliferation was associated with the induction of insulin receptor substrate-2 and pancreatic homeodomain protein-1 via the activation of the cAMP response element binding protein. Estrogen replacement and exercise shared a common pathway, which led to the improvement of beta-cell function and mass, via cAMP response element binding protein activation, explaining the lack of an additive effect with combined treatments. In conclusion, decreased beta-cell mass leading to impaired insulin secretion triggers glucose dysregulation in estrogen insufficiency, regardless of body fat. Regular moderate exercise eliminates the risk factors of contracting diabetes in the postmenopausal state.

Experimental study of an automated system for the delivery of eyedrops using a microinfusion pump.

PURPOSE: To determine the feasibility of using a commercially available microinfusion pump for the continuous delivery of eye drops using a rabbit model. DESIGN: Laboratory investigation. METHODS: Tear secretion was measured after attaching a microinfusion pump to the superior fornix of a rabbit. The pump was set to deliver artificial tears continuously. A rabbit eye was first chemically burned with 1N NaOH, the pump was then set to deliver 0.1% fluorometholone continuously. Results were compared with those obtained using 0.1% fluorometholone. RESULTS: Schirmer tests indicated that an average of 22.3 mm in eyes supported by a pump and an average of 10.3 mm in eyes without pump. Moreover, eyes treated with corticosteroid delivered by pump recovered faster than those treated with topical corticosteroid. CONCLUSIONS: The continuous delivery of eye drops by a microinfusion pump could be applicable to patients with severe dry eyes or ocular surface diseases. Further study should be needed.

Improvement of insulin resistance and insulin secretion by water extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% pancreatectomized rats.

The effect of supplementation with Phellinus linteus (P. linteus), Paecilomyces tenuipes (P. tenuipes), and Cordyceps militaris (C. militaris) mushroom water extracts on the insulin secretion and insulin resistance of 90% pancreatectomized (Px) male Sprague Dawley rats was investigated. Px rats were daily administered 0.5 g of P. linteus, P. tenuipes, and C. militaris aqueous extracts or a placebo per 1 kg body weight with a 40% fat diet for 8 weeks. Fasting serum glucose levels were lower in rats receiving C. militaris than in the control group. Insulin secretion at the elevated serum glucose levels was lowest in rats that consumed P. tenuipes in hyperglycemic clamp. Whole body glucose disposal rates increased in C. militaris but decreased in P. tenuipes compared to those in the control group in euglycemic hyperinsulinemic clamp. The GLUT4 content and fraction velocity of glycogen synthase in the soleus and quadriceps muscles increased in the rats treated with C. militaris, but P. tenuipes decreased both. In sum, a water extract of C. militaris ameliorates insulin resistance by enhancing glucose utilization in skeletal muscles.