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"Nonetheless, given that intranasal insulin delivery in 30 min is sufficient to elevate insulin levels in cerebrospinal fluid, these findings are in line with previous reports in rats and dogs, suggesting that direct brain insulin infusion lowers plasma glucose levels independently of changes in food intake."
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"Osteocalcin knockout mice exhibited glucose intolerance, increased fat mass, insulin resistance, decreased expression of insulin target genes in liver and muscle, and decreased adiponectin gene expression in adipose [XREF_BIBR], while administration of recombinant osteocalcin increased insulin secretion, decreased blood glycaemia and weaken the development of obesity [XREF_BIBR]."
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"Later studies have also confirmed the above findings, where gestational low protein (6% vs. 20% in control) in rats led to insulin resistance in adult offspring by involving an inadequate insulin induced phosphorylation of the Insulin receptor, insulin receptor substrate-1 (IRS-1) and Akt substrate of 160kDa (AS160) as well as an impaired GLUT4 translocation and the corresponding increases in glucose and insulin levels when subjected to an IGTT (Blesson etal., 2014)."
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"Furthermore, research with isolated human islets has consistently shown that beta-cells from type 2 diabetic subjects display several defects that include reduced insulin content, diminished insulin mRNA expression, and decreased, or absent, first-phase insulin secretion in response to glucose."
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"With increased glucose supply, the peak (at 0 h, P = 0.01) and increment of insulin (P = 0.02) were linearly increased in accordance with the significantly increased area under the curve in 240 min after infusion (P = 0.05), indicating a sustained high level of blood insulin in high glucose supply (G80 and G100) compared with low glucose supply (G0 and G20)."
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"XREF_BIBR, XREF_BIBR It is also known that insulin resistance and hyperinsulinemia, which are problems associated with type 2 DM, can induce low insulin levels in the central nervous system which are closely associated with the onset of AD through reduction of cerebral blood flow, accumulation of amyloid-beta, phosphorylation of tau protein and so on."
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"Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase."
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"To examine whether our ICV insulin injection protocol induced an increase of the insulin level in physiological ranges, we measured the OB and plasma insulin levels in both 22 h fasted and satiated animals receiving a NaCl ICV injection (respectively Fasted-NaCl and Satiated-NaCl animals) and in 22 h fasted animals receiving a 14 mU insulin ICV injection (Fasted-Insulin animals) (XREF_FIG)."
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"Another study showed the potential for combining ADSCs treatment with gene therapy by transducing ADSCs with a furin-cleavable insulin gene (INS-FUR), which led to enhanced insulin expression in the differentiated adipocytes, and alleviated hyperglycemia in diabetic mice [XREF_BIBR]."
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"Insulin producing cells generated from embryonic stem cells, when treated with exendin-4, augmented their insulin expression more than five-fold [XREF_BIBR], suggesting the possibility that embryonic stem cells may express GLP-1 receptor and that GLP1 may have a role in recruitment and differentiation of progenitor cells during pancreatic development."
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"The results of the present study, using the conscious beagle dog, demonstrate that inhaled insulin (INH; Exubera) provides better glycemic control during an intraportal glucose load than identical insulin levels induced by insulin (Humulin) infusion into the inferior vena cava (IVC)."
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"Insulin resistance was defined as fasting insulin> 10mU/ml, or HOMA-IR> 1.66, or abnormal insulin release curve (insulin peak more than ten times the basic value; insulin peak delayed to 1h after taking sugared water; area under the insulin curve increased; insulin level not returning to the normal fasting level 3h after taking sugared water), but with normal fasting blood glucose and glucose tolerance levels [XREF_BIBR]."
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"Insulin secretory capacity was reduced by 60% in vitamin D receptor knockout mice [152] with increased post-challenged blood glucose but normal fasting blood glucose concentration and reduced insulin mRNA levels in pancreatic islets but normal pancreatic beta cell mass, islet architecture, and islet neogenesis when compared to wild type mice."
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"Interestingly, it was shown that high peripheral insulin concentrations acutely increase the levels of insulin in the brain and the cerebrospinal fluid (CSF), whereas prolonged peripheral hyperinsulinemia leads to a down-regulation of IRs in the BBB and to a reduction in insulin transport into the brain."
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"Some of the beneficial effects of cathepsin K knockout on cardiac hypertrophy may be attributed to its ability to alleviate insulin resistance, as evidenced by inhibition of high-fat diet induced elevated cardiac phospho-Akt and insulin receptor-beta, reversal of the blunting of cardiac insulin stimulated Akt phosphorylation, and increased insulin stimulated Akt phosphorylation and improved serum glucose and insulin levels."
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"We conclude that (1) the pharmacokinetic behavior of regular insulin depends primarily on its route of administration; (2) continuous IV infusion of an insulin dose causes significantly higher serum insulin levels than the SC administration of the identical insulin dose, and (3) hyperinsulinemia caused by a square wave insulin infusion (12.8 U/hr; time : 0 to 17 minutes) requires more than four times longer to return to baseline levels following SC administration than after IV administration of the insulin."
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"In this method, the antibodies fixed to the test tube may be saturated with insulin when the serum insulin is too dense, and unbound insulin and signal antibodies may be combined, leaving only a small amount of signal antibodies after washing, thus causing an underestimation of the insulin level, referred to as the high-dose hook effect."
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"During the test period, low-dose insulin infusion kept plasma insulin at basal levels in C and C (TG) and high-dose insulin infusion increased plasma insulin levels about 6 times the baseline insulin level in C. Glucose infusion rate (GIR) was significantly higher in rats with high insulin infusion than those with low insulin infusion."
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"In the HF groups with B. thetaiotaomicron or lactitol supplementation, the acute insulin responses were attenuated, showing decreased insulin levels at time point 1h, when compared to the fasting values of the same group [p = 0.0004 and p = 0.012, respectively (Student 's t-test)]."
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"Insulin therapy is commonly initiated with a strategy to increase a patient 's endogenous basal insulin level with injected basal insulin, administered as a once-daily, long acting insulin analogue preparation or as an injection of intermediate acting human insulin administered once- or twice-daily (XREF_FIG)."
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"Some suggest that hepatic deposition of lipid is not a primary process but a " normal " response to elevated circulating insulin levels induced by muscle insulin resistance and thus that hepatic steatosis, typically found in obese adolescents with the metabolic syndrome, is the result and not one of the culprits of the adverse metabolic phenotype characteristic of insulin resistant individuals."
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"This clearly suggests the need for extreme caution while preparing food for diabetic individuals to ensure it has not just low GI but also a low insulin index to avoid raising insulin levels in the blood; high insulin concentration is associated with insulin resistance and cardiac risk."
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"BAY 55-9837 stimulated glucose dependent insulin secretion in isolated rat and human pancreatic islets, increased insulin synthesis in purified rat islets, and caused a dose dependent increase in plasma insulin levels in fasted rats, with a half-maximal stimulatory concentration of 3 pmol/kg."
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"Insulin tolerance tests at week 7 showed that both insulin treatments significantly reduced glucose concentrations and increased insulin levels compared with the Sham group, CRI significantly reduced glucose at 4 and 6h relative to Reg-In (P < 0.05), suggesting the effects of CRI on reducing glucose last longer than Reg-In."
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"XREF_BIBR A single exercise bout reversed the insulin sensitivity of diet induced obese rats and reduced the expression of inducible nitric oxide synthase and s nitrosation of insulin receptor and insulin receptor substrate 1/protein kinase B, accompanied by an increase in the activity of 5 ' adenosine monophosphate activated protein kinase (AMPK)."
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"Insulin resistance appears to have a pivotal role with multiple studies demonstrating significant associations between altered lipid metabolism and insulin level, which may be induced in part by the insulin medicated stimulation of lipolysis and altered expression of lipoprotein lipase and hepatic lipase [XREF_BIBR, XREF_BIBR]."
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"In the silk hydrogel, islets with both collagen IV and laminin showed a significant increase in beta-cell insulin gene expression, but not enhanced insulin protein secretion compared to islets in silk in the absence of ECM proteins (illustrated by XREF_FIG and XREF_FIG respectively)."
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"In light of these considerations, we utilized insulin’s effect on expression of genes in lipogenic pathways to assess hepatic insulin resistance.Ad libitum intake of the HF diet suppressed the effects of an oral glucose load, used to raise plasma insulin level, on expression of some of the genes studied (Srebf1, Fasn, Scd1, Gck, Pck1, and Cpt1a)."
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"Measurement of serum insulin levels (XREF_FIG) confirmed that insulin treatment by minipump continuous infusion increased the circulating insulin levels of diabetic mice (STZ+INS and STZ+BOTH); and at the end of the study period, insulin values in these groups were not statistically different from control mice (1 vs. 4 or 2 vs. 6, NS); however, insulin concentrations in groups 1, 2, 3 and 5 reflect endogenous mouse insulin production, whereas values for groups 4 and 6 primarily quantify exogenous delivery of human insulin."
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"Elevated circulating insulin level induced by insulin resistance could contribute to the development of endometrial cancer by promoting cell proliferation through the PI3K and AKT and Ras and MAPK pathways and leading to changes in sex hormone levels in direct or indirect way XREF_BIBR."
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"Since adiponectin increases, while resistin and pro-inflammatory cytokines decrease insulin sensitivity, altogether these changes in the cytokine and adipokine expressions decrease whole-body insulin sensitivity leading to compensatory increases in circulating plasma insulin levels and later to the development of type-2 diabetes mellitus ."
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"By means of a primed-continuous insulin infusion (100mU/kgmin -1 within 3min, then 3.5 mU/kgmin -1, Humulin-R, Eli Lilly, Indianapolis), insulin levels were acutely raised and maintained at a physiological level until 120min (" steady state " conditions, pmol/l : 372 +/-86 Irp2 -/- vs. 374 +/-64 in WT), as previously described XREF_BIBR, XREF_BIBR."
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"It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population."
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"Insulin resistance is characterized by the inability of insulin to suppress hepatic glucose output, which is caused by sustained elevation of gluconeogenesis in the liver, and impaired insulin-stimulated glucose uptake in muscle and adipose tissues, which is caused by defective glucose transporter type 4 (GLUT4) cell surface expression in these tissues [70]."
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"Interestingly, alphaIRKO islets exhibited a significantly higher insulin gene expression in response to high glucose stimulation, and the addition of 100 nM insulin to the high glucose stimulation media further enhanced insulin gene expression in the alphaIRKO islets, but not in the controls, suggesting that beta-cells in alphaIRKO islets are more sensitive to insulin (XREF_FIG)."
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"These data are also in keeping with a recent study in rats, in which experimental hyperinsulinemia (i.e., insulin infusion to raise insulin levels by approximately 66%) was started at age 28 days and continued for 4 weeks (encompassing the time of puberty, since vaginal opening occurred by 40 days of age)."
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"However, inoculation of such SV40 transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography."
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"Insulin infusion markedly increased plasma insulin levels at the end of the clamp for both genotypes (0.9 +/- 0.3 vs. 7.7 +/- 0.4 ng/mL for basal vs. insulin stimulated conditions in Stk25 -/- mice [P < 0.01] and 1.5 +/- 0.3 vs. 7.8 +/- 0.3 ng/mL for basal vs. insulin stimulated conditions in wild-type mice [P < 0.01]), with no significant differences between the genotypes."
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"Third, we could not measure the INS levels in CNS directly; therefore, it is possible that the 40 units INS caused the heterogeneous elevation of INS levels in CNS among the subjects, and the differences in the INS levels in CNS might have affected the results in the present study; however, we adopted the INS dose according to that used in a previous report, which verified the high INS levels in CSF using the same dose of INS as that administered in our study [13]."
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"In part III of the experiment both insulin and somatostatin were infused for the final 2 h. Plasma insulin levels were increased by insulin infusion (to 0.1476 to 0.1290 i.u./l for parts I and III respectively) and were reduced by somatostatin infusion in part II (to 0.006 i.u./l) relative to the basal periods (mean 0.021 i.u./l)."
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"Finally, we provided results to suggest that the transdifferentiated cells are functional by detecting : (1) functional markers for pancreatic beta-cells including prohormone convertase 1/3 (PC1/3), insulin C-peptide and glucagon like peptide 1 receptor (GLP-1R), (2) increased insulin mRNA expression after treatment of cells with GLP-1 and betacellulin, physiological stimuli that regulate pancreatic function and (3) elevated insulin secretion after glucose challenge."
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"Two weeks of insulin therapy (euglycemia) starting six weeks after the onset of diabetes, increased body mass and plasma insulin level, and lowered blood glucose,% hemoglobin glycosylation, serum SSAO, and thiobarbituric acid reactants to near control, non diabetic levels, establishing that seen were the result of diabetes and not from STZ toxicity."
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"The development of FK506 induced PTDM may be multifactorial : (1) insulin secretion impairment consequent to either decreased insulin expression or lower secretory capacity in beta cells; (2) altered glucokinase function, lowering the efficiency of glucose induced insulin secretion; (3) increased apoptosis in the islets; and (4) other uncharacterized effects."
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"However, another study found that patients with regular insulin use presented with better memory function after 2 and 4 months compared with patients receiving a placebo; this is likely because insulin administration increases brain insulin levels and improves memory and cognition in MCI or early stages of AD, which leads to enhanced Abeta clearance from the brain."
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"An attractive hypothesis that could explain the differences in IR isoform localization and function in the selective insulin dependent up-regulation of insulin and betaGK gene expression via IR-A and IR-B, respectively, is signal transduction from different microdomains within the beta-cell plasma membrane."
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"Notably, the β-cell-specific Chop gene depletion mouse model produced similar results to mice with reduced insulin synthesis, in that the pancreatic β-cells not only show reduced ER stress but also had reduced insulin mRNA expression and delayed insulin secretion under physiological glucose levels138."
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"Insulin resistance in the classical target organs for this hormone (liver, muscle, and adipose tissue) leads to increase circulating levels of insulin, which would then have amplified effects on other tissues, with the kidney being particularly sensitive, as it is by far the most perfused organ of the body."
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"Glucose fed rats displayed higher plasma levels of glucose and insulin, insulin resistance, arterial hypertension, enhanced production of superoxide anion (O 2 *-) in the heart and aorta XREF_BIBR, XREF_BIBR, XREF_BIBR and pain polyneuropathy as assessed by the presence of tactile and cold allodynia XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"To examine whether decreased insulin secretion during starvation is related to a change in the ability of insulin to inhibit its own secretion, plasma C-peptide was measured after plasma insulin levels were acutely raised by intravenous (IV) insulin infusion in a dose of 40 and 80 mU/M2/min in obese subjects before and after a 72 hour fast."
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"Insulin resistance causes an increase in both plasma glucose and serum insulin levels.9 Hyperglycemia causes hyperosmolarity, leading to fluid shift from the intracellular compartment to the extracellular compartment, which results in plasma volume expansion.10 Hyperinsulinemia causes an increase of sodium reabsorption from renal tubules, renin secretion, and sympathetic nervous activity.11 Thus, elevated circulating levels of both glucose and insulin themselves could be a direct mediator of BP elevation in insulin resistance."
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"However, these mice appeared to be in a state of insulin resistance exhibiting two-fold raised plasma insulin levels, decreased triglyceride hydrolysis and increased fat deposition in adipose tissue, as well as delayed glucose clearance due to slower uptake in skeletal muscle [XREF_BIBR]."
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"Despite whole body insulin resistance, in isolated vastus lateralis muscle, basal and insulin stimulated 3-O-methylglucose transport, as well as protein expression of the insulin or exercise-regulatable glucose transporter, GLUT-4, and glycogen content were comparable between the patients and controls."
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"When the plasma insulin level of ob/ob mice was increased threefold by the administration of neutral protamine Hagedorn (NPH) insulin, the in vitro stimulatory effect of insulin on [14C] glucose oxidation by adipose tissue isolated from these animals was not altered, suggesting that insulin induced receptor or postreceptor changes do not account for the increased insulin resistance produced by RCM-hGH."
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"Using a novel form of insulin conjugated with chromium - CRI and Reg-In treated KKAy mice, we observed that both insulin treatments significantly reduced glucose concentrations and increased insulin levels compared with the Sham group, and there was no difference in glucose levels in 2h between two insulin groups."