Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia

1993 ◽  
Vol 265 (3) ◽  
pp. E446-E453 ◽  
Author(s):  
T. R. Pieber ◽  
D. T. Stein ◽  
A. Ogawa ◽  
T. Alam ◽  
M. Ohneda ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Dependent Diabetes Mellitus ◽  
Male Rats ◽  
In Vivo Studies ◽  
Dependent Diabetes Mellitus ◽  
Ru 486 ◽  
Insulin Resistant ◽  
Insulin Dependent

To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM. In obesity-associated and dexamethasone-induced insulin resistance without diabetes, basal and stimulated secretion of amylin and insulin by isolated pancreata were proportionately elevated, leaving the amylin-to-insulin ratio (A/I) unchanged. By contrast, whenever diabetes occurred in dexamethasone-treated rats or in spontaneously diabetic obese insulin-resistant ZDF-drt male rats, a doubling of A/I was invariably observed due to an increase in amylin without a proportional increase in insulin secretion. Correction of dexamethasone-induced hyperglycemia with the glucocorticord receptor antagonist RU-486 was accompanied by a decline in A/I. Longitudinal in vivo studies demonstrated in both spontaneous and dexamethasone-induced models of NIDDM an increase in plasma A/I at the onset of hyperglycemia. In dexamethasone-induced diabetes, the increased A/I was associated with a high proamylin mRNA relative to proinsulin mRNA. We conclude that amylin and insulin expression and secretion rise in concert in compensated insulin-resistant states, but when hyperglycemia is present the increase in amylin exceeds that of insulin. Although a role of an increased A/I in the pathogenesis of NIDDM has not been established directly, these studies indicate that such a role could be possible.

Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM

1987 ◽  
Vol 253 (3) ◽  
pp. E300-E304 ◽  
Author(s):  
H. Yki-Jarvinen ◽  
K. Kubo ◽  
J. Zawadzki ◽  
S. Lillioja ◽  
A. Young ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
American Indians ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Binding ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Insulin Dependent ◽  
Obese Subjects

It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. We compared the sensitivities of glucose transport and antilipolysis to insulin and measured insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic (% fat, 41 +/- 1), 25 obese diabetic (% fat, 40 +/- 1), and 15 nonobese (% fat, 30 +/- 1) female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport and antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED50 for stimulation of glucose transport was higher in the obese patients with NIDDM (171 +/- 38 vs. 92 +/- 10 pM, P less than 0.005). In contrast, the ED50s for antilipolysis were similar in obese diabetic patients (32 +/- 6 pM) and obese nondiabetic subjects (27 +/- 3 pM). No difference was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder.

scholarly journals Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases?

2004 ◽  
Vol 50 (11) ◽  
pp. 2136-2140 ◽  
Author(s):  
Marie Bennermo ◽  
Claes Held ◽  
Sten Stemme ◽  
Carl-Göran Ericsson ◽  
Angela Silveira ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Promoter Region ◽  
Insulin Dependent Diabetes Mellitus ◽  
Juvenile Chronic Arthritis ◽  
In Vivo Studies ◽  
Dependent Diabetes Mellitus ◽  
Tnf Α

Abstract Background: A single-nucleotide polymorphism (SNP) in the promoter region of the interleukin-6 (IL-6) gene at position −174 (G>C) has been reported to be associated with a variety of major diseases, such as Alzheimer disease, atherosclerosis, and cardiovascular disease, cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis, and systemic-onset juvenile chronic arthritis. However, authors of previous in vitro and in vivo studies have reported conflicting results regarding the functionality of this polymorphism. We therefore aimed to clarify the role of the −174 SNP for the induction of IL-6 in vivo. Methods: We vaccinated 20 and 18 healthy individuals homozygous for the −174 C and G alleles, respectively, with 1 mL of Salmonella typhii vaccine. IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured in the blood at baseline and up to 24 h after vaccination. Results: Individuals with the G genotype had significantly higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did individuals with the C genotype (P <0.005). There were no differences between the two genotypes regarding serum concentrations of IL-1β and TNF-α before or after vaccination. Conclusions: The −174 G>C SNP in the promoter region of the IL-6 gene is functional in vivo with an increased inflammatory response associated with the G allele. Considering the central role of IL-6 in a variety of major diseases, the present finding might be of major relevance.

Metabolic effects of vanadyl sulfate in humans with non—insulin-dependent diabetes mellitus: In vivo and in vitro studies

Metabolism ◽  
2000 ◽  
Vol 49 (3) ◽  
pp. 400-410 ◽  
Author(s):  
Allison B. Goldfine ◽  
Mary-Elizabeth Patti ◽  
Lubna Zuberi ◽  
Barry J. Goldstein ◽  
Raeann LeBlanc ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
In Vitro Studies ◽  
Insulin Dependent Diabetes ◽  
Vanadyl Sulfate ◽  
Metabolic Effects ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

Increased activity of the hexosamine synthesis pathway in muscles of insulin-resistant ob/ob mice

1997 ◽  
Vol 272 (6) ◽  
pp. E1080-E1088 ◽  
Author(s):  
M. G. Buse ◽  
K. A. Robinson ◽  
T. W. Gettys ◽  
E. G. McMahon ◽  
E. A. Gulve
Keyword(s):  
Insulin Resistance ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Hexosamine Biosynthetic Pathway ◽  
Insulin Resistant ◽  
Hindlimb Muscles ◽  
Glucose Flux ◽  
Hexosamine Pathway ◽  
Insulin Dependent ◽  
And Control

Enhanced glucose flux via the hexosamine biosynthetic pathway has been implicated in insulin resistance. We measured products of this pathway, UDP-N-acetyl hexosamines (UDP-HexNAc), and activity of the rate-limiting enzyme L-glutamine:D-fructose-6-phosphate amidotransferase (GFAT) in tissues of ob/ob mice and lean controls. Ob/ob mice were obese, hyperglycemic, and hyperinsulinemic. Resistance to the effect of insulin on glucose transport was demonstrated in isolated soleus muscles, although total GLUT-4 concentration was mildly increased in muscles from ob/ob mice. UDP-HexNAc concentrations in hindlimb muscles decreased between 8 and 17 wk but were always higher in ob/ob vs. controls (P < 0.001, mean increase 67%). Concentrations of UDP-hexoses and GDP-mannose were similar in ob/ob and control muscles. Muscle GFAT activity declined with age but was increased in ob/ob vs. controls at each age examined (P < 0.001, mean increase 108%). UDP-HexNAc concentrations and GFAT activity were similar in livers of ob/ob and controls. These data suggest that glucose flux via the hexosamine pathway is selectively increased in muscle but not liver of ob/ob mice and may contribute to muscle insulin resistance in this model of non-insulin-dependent diabetes mellitus.

Glycaemic responses to cereal-based Indian food preparations in patients with non-insulin-dependent diabetes mellitus and normal subjects

2000 ◽  
Vol 83 (5) ◽  
pp. 483-488 ◽  
Author(s):  
Asna Urooj ◽  
Shashikala Puttaraj
Keyword(s):  
Diabetes Mellitus ◽  
Area Under The Curve ◽  
Normal Subjects ◽  
Insulin Dependent Diabetes Mellitus ◽  
Glycaemic Index ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

The in vivo glycaemic responses to six cereal-based foods traditionally consumed in South India were evaluated in patients with non-insulin-dependent diabetes mellitus (NIDDM) and healthy volunteers. All foods contained 50 g carbohydrate and were compared with a 50 g glucose load. Also studied were the in vitro starch digestibility and nutrient composition of the foods. The postprandial responses to the foods at 30, 60 and 120 min were significantly (P < 0·05) lower than those to the reference glucose, in both groups. The peak glucose responses for three foods, i.e. chapatti, idli and poori, occurred 60 min postprandially in both groups. The glycaemic index (GI) values ranged from 67 to 90 in NIDDM and from 44 to 69 in healthy subjects with no significant differences within the groups. Significant relationships were observed between peak responses and area under the curve for foods in patients with NIDDM and in vitro rate of starch hydrolysis (r 0·83, r 0·85, P < 0·05). The GI values predicted using in vitro data were found to be similar to the GI values observed in patients with NIDDM. The GI concept is useful for identifying foods in the habitual Indian diet with attributes of the desired glycaemic effect such as delayed peak rise and low area under the curve.

Platelet cNOS Activity Is Reduced in Patients with IDDM and NIDDM

1998 ◽  
Vol 79 (03) ◽  
pp. 520-522 ◽  
Author(s):  
Guido Bruno ◽  
Fulvia Trucco ◽  
Elena Zumpano ◽  
Milena Tagliabue ◽  
Cataldo Di Bisceglie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Normal Subjects ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
No Production ◽  
Insulin Dependent

SummarySeveral studies in vitro and in vivo suggest that the nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to vascular alteration facilitating platelet-vascular wall interaction, adhesion of monocytes to endothelium, vascular smooth muscle proliferation and by decreasing endothelium-dependent vasodilation. In this study we evaluated the activity of the constitutive nitric oxide synthase (cNOS) in platelets of patients with insulin-dependent diabetes mellitus (IDDM) and with non-insulin-dependent diabetes mellitus (NIDDM). When compared to that of normal subjects, cNOS activity is significantly lower in patients with IDDM and with NIDDM (1.57 ± 0.25 vs. 0.66 ± 0.10 fmol/min/10 9 PLTs and 1.57 ± 0.25 vs. 0.67 ± 0.08, respectively; p <0.005). These data demonstrate that the platelet cNOS activity is decreased in diabetes mellitus.

Evidence for pancreatic pacemaker for insulin oscillations in low-frequency range

1994 ◽  
Vol 266 (6) ◽  
pp. R1786-R1791 ◽  
Author(s):  
H. F. Chou ◽  
N. Berman ◽  
E. Ipp
Keyword(s):  
High Frequency ◽  
Serum Insulin ◽  
Low Frequency ◽  
Mean Amplitude ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
Rat Islets Of Langerhans

Circulating insulin concentrations oscillate in regular fashion, with periods that fall into a high-frequency (period of 5-17 min) or low-frequency (period of 50-150 min) range. Only the high-frequency oscillations have so far been reported in vitro, suggesting that these derive from a primary pancreatic source. This study tested whether the low-frequency insulin oscillations could also be identified in vitro. Rat islets of Langerhans were perifused for 20 h using RPMI medium with 5.5 mM glucose. Perifusate fractions were collected at 9.9-min intervals. Mean insulin concentrations at the outset were 21.4 +/- 2.9 microU/ml, increased to 32.5 +/- 4.6 (P < 0.05) between 13 and 17 h after the start of perifusion, and then either leveled off or decreased to baseline. Superimposed on this general trend, we found sustained insulin oscillations with a period of 50-100 min. The mean amplitude was 14.2 +/- 4.2 microU/ml, and the amplitude/mean ratio was 64.6 +/- 12%. Spectral analysis revealed significant peaks at periods that were close to either 50 or 100 min and a smaller peak at 24-37 min. These data, using in vitro methodology and constant glucose concentrations, indicate the presence of sustained, spontaneous, low-frequency, ultradian insulin oscillations in the pancreatic islets. This provides evidence for a pancreatic component that may participate in the previously described in vivo ultradian insulin oscillations. This finding may also provide a mechanism for the apparent escape from glucose entrainment of serum insulin oscillations in non-insulin-dependent diabetes mellitus.

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