Trying to find an answer to Dawn Phenomena or liver dumps
Question:
>Fish oil prevents insulin resistance induced by high-fat >feeding in rats.
Wouldn’t this just be if you eat a LOT of it? I use Omega 3′s and fish oil to lower cholesterol…. Linda
Response:
>Here’s the link to the full text article with an abstract >below: >http://ajpendo.physiology.org/cgi/content/full/273/4/E708 >Obesity is associated with both insulin resistance and >hyperinsulinemia. Initially hyperinsulinemia compensates for >the insulin resistance and thereby maintains normal glucose >homeostasis.
How do you know if you have too much insulin, or not enough, if you are a type 2? Linda
Response:
Not sure, Dazey. My preliminary findings in this research is that the Omega 3′s may have part of the answer for us. I love salmon anyway, so I"m just eating much more of it weekly. Bonita
– Hide quoted text — Show quoted text ->Fish oil prevents insulin resistance induced by high-fat >feeding in rats. > Wouldn’t this just be if you eat a LOT of it? I use Omega 3′s and > fish oil to lower cholesterol…. > Linda
Response:
I dunno, Linda. I’ve just learned in the past two days that T2′s are known to have hyperinsulinemia, or too much damn insulin floating around their systems. I always assumed that my pancreas was failing and not putting out enough insulin thereby making the doctors give me meds to compensate by pancreas stimulation drugs. This too much insulin issue really stumps me because after six years, I figure somebody down the line might have checked my insulin levels before throwing drugs at me. Bonita
– Hide quoted text — Show quoted text ->Here’s the link to the full text article with an abstract >below: >http://ajpendo.physiology.org/cgi/content/full/273/4/E708 >Obesity is associated with both insulin resistance and >hyperinsulinemia. Initially hyperinsulinemia compensates for >the insulin resistance and thereby maintains normal glucose >homeostasis. > How do you know if you have too much insulin, or not enough, if you > are a type 2? > Linda
Response:
Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Hotamisligil GS, Johnson RS, Distel RJ, Ellis R, Papaioannou VE, Spiegelman BM. Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. CA 92093, USA. Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2-/- animals failed to express in adipose tissue tumor necrosis factor-alpha (TNF-alpha), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-alpha. PMID: 8910278 [PubMed - indexed for MEDLINE]
Response:
Metabolic implications of body fat distribution. Bjorntorp P. Department of Medicine I, University of Goteborg, Sahlgren’s Hospital, Sweden. Insulin resistance is the cornerstone for the development of non-insulin-dependent diabetes mellitus (NIDDM). Free fatty acids (FFAs) cause insulin resistance in muscle and liver and increase hepatic gluconeogenesis and lipoprotein production and perhaps decrease hepatic clearance of insulin. It is suggested that the depressing effect of insulin on circulating FFA concentration is dependent on the fraction derived from visceral adipocytes, which have a low responsiveness to the antilipolytic effect of insulin. Elevated secretion of cortisol and/or testosterone induces insulin resistance in muscle. This also seems to be the case for low testosterone concentrations in men. In addition, cortisol increases hepatic gluconeogenesis. Cortisol and testosterone have "permissive" effect on adipose lipolysis and therefore amplify lipolytic stimulation; FFA, cortisol, and testosterone thus have powerful combined effects, resulting in insulin resistance and increased hepatic gluconeogenesis. All these factors promoting insulin resistance are active in abdominal visceral obesity, which is closely associated with insulin resistance, NIDDM, and the "metabolic syndrome." In addition, the endocrine aberrations may provide a cause for visceral fat accumulation, probably due to regional differences in steroid-hormone-receptor density. In addition to the increased activity along the adrenocorticosteroid axis, there also seem to be signs of increased activity from the central sympathetic nervous system. These are the established endocrine consequences of hypothalamic arousal in the defeat and defense reactions. There is some evidence that suggests an increased prevalence of psychosocial stress factors is associated with visceral distribution of body fat. Therefore, it is hypothesized that such factors might provide a background not only to a defense reaction and primary hypertension, suggested previously, but also to a defeat reaction, which contributes to an endocrine aberration leading to metabolic aberrations and visceral fat accumulation, which in turn leads to disease. Publication Types: a.. Review b.. Review, Academic PMID: 1773700 [PubMed - indexed for MEDLINE]
Response:
[Health risks of obesity. Significance of the regional distribution of adipose tissue] [Article in Danish] Richelsen B. Arhus Amtssygehus, medicinsk-endokrinologisk afdeling III. This review concentrates on recent prospective studies concerning evaluation of the health risk of obesity with special reference to the impact of the distribution of the adipose tissue. Analysis of the data indicates that adipose tissue localized to the abdominal region (especially intraabdominal fat) is associated with an enhanced risk profile including elevated levels of triglycerides and insulin, low levels of high density lipoprotein-cholesterol and elevated blood pressure. Abdominal obesity, determined by the waist/hip ratio, was associated with cardiovascular disease, premature death and non-insulin demanding diabetes mellitus. On the other hand, the total fat mass (measured as body mass index) was positively associated only with non-insulin demanding diabetes mellitus. The androgen/estrogen activity seems to be an important factor for determining the topographical localization of the adipose tissue. The great amount of free fatty acids which may be released from the abdominal fat tissue seemed to be of great pathogenetic importance for the metabolic consequences of abdominal obesity. In conclusion, obesity and the abdominal localization of adipose tissue seem to be two separate entities with different pathogenesis and clinical consequences. The abdominal obesity is the type which is predominantly associated with enhanced health risks. These associations may result in an altered strategy of treatment of the obese population. Publication Types: a.. Review b.. Review, Tutorial PMID: 2024293 [PubMed - indexed for MEDLINE]
Response:
Regulation of nutrient metabolism and energy expenditure. Felber JP, Golay A. Institute of Physiology, University of Lausanne, Switzerland. The requisites for energy expenditure are covered mainly by two major substrates, glucose and free fatty acids (FFA). Their regulation and metabolism differ. After carbohydrate ingestion, glucose is rapidly oxidized or stored in muscles and liver. There is a constant alternance between glucose storage as glycogen after meals and glycogen mobilization in the postabsorptive state when plasma glucose has returned to the basal state. Impairment of this alternance, in particular when glycogen stores are not being used, may lead to glucose intolerance and insulin resistance. Ingestion of lipids is not followed by an immediate increase in lipid oxidation, but FFA are stored as triglycerides in different tissues. Lipolysis occurs in the fasting state from tissue triglycerides and favors lipid oxidation. Lipid oxidation is typically increased in obesity. The preferential use of FFA from triglyceride stores for energy expenditure in obesity is responsible for the decrease in glucose mobilization from glycogen stores. This leads to a negative feedback of muscle and liver glycogen on glycogen synthase activity and consequently on glucose storage. It results in glucose intolerance after carbohydrate ingestion. Diabetes develops in obesity, usually after a long period of glucose intolerance, when glycemia does not return to the basal state. In obesity, glucose intolerance and insulin resistance can be prevented, or if already existing, can be decreased by stimulating glycogen mobilization by exercise, thermogenesis-stimulating drugs, and weight loss, which reduces fat stores and decreases lipid oxidation. Publication Types: a.. Review b.. Review, Tutorial PMID: 7869936 [PubMed - indexed for MEDLINE]
Response:
Bjorntorp P. Department of Heart and Lung Diseases, Sahlgren’s Hospital, Goteborg, Sweden. Abdominal obesity in man is an integrated part of the Metabolic Syndrome, and is associated with a complex neuroendocrine disturbance. Its consequences for the metabolism of the periphery seems to be insulin resistance caused by a combination of a relative hypercortisolaemia and a relative deficiency of sex steroid hormones. This hormonal aberration, in combination with a relative insufficiency of growth hormone secretion, might also direct depot triglycerides to visceral adipose tissues, a consequence at least partly due to varying densities of the specific receptors for these hormones. Visceral fat accumulation may thus be a consequence of the neuroendocrine aberrations, and may amplify the metabolic symptoms via effects on the liver of free fatty acids released in abundance from the lipolytically sensitive enlarged visceral fat depots. The origin of the neuroendocrine disturbance is not known, but epidemiological and cross-sectional information suggest that psychosocial factors are intimately involved. Animal and human studies indicate that the mediating factor(s) may be stress-sensitivity, leading to the neuroendocrine consequences observed. Publication Types: a.. Review b.. Review, Tutorial PMID: 1485940 [PubMed - indexed for MEDLINE]
Response:
Disordered metabolism in diabetes: have we underemphasized the fat component? McGarry JD. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235. Despite intensive investigation, a clear understanding of the metabolic disturbances in diabetes mellitus and their temporal relationship to each other during disease development has still not emerged. With emphasis on non-insulin-dependent diabetes (NIDDM), three possibilities are explored here: (1) that the insulin resistance characteristic of obesity/NIDDM syndromes is the result rather than the cause of hyperinsulinemia, as is widely held, (2) that the linkage between hyperactivity of the pancreatic beta-cell and peripheral insulin resistance is vested in excessive delivery of lipid substrate from liver to the muscle bed, and (3) the conceivably hyperamylinemia works in concert with hyperinsulinemia in promoting overproduction of very-low-density lipoproteins by the liver, and thus in the etiology of muscle insulin resistance. Publication Types: a.. Review b.. Review, Tutorial PMID: 7929616 [PubMed - indexed for MEDLINE]
Response:
Interaction between free fatty acids and glucose metabolism. Boden G. Division of Endocrinology/Diabetes/Metabolism and the General Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.. PURPOSE OF REVIEW: The prevalence of obesity and of type 2 diabetes mellitus are increasing at an accelerating rate in the USA and other industrialized countries. Free fatty acids (FFAs) have emerged as a major link between obesity and insulin resistance/type 2 diabetes mellitus. A review of the interaction between FFAs and glucose metabolism is therefore timely and relevant. RECENT FINDINGS: Acute and chronic elevations in plasma FFAs produce peripheral (muscle) and hepatic insulin resistance. In skeletal muscle, this process is associated with accumulation of intramyocellular triglyceride and diacylglycerol, and with activation of protein kinase C (the beta and delta isoforms). It is hypothesized that FFAs interfere with insulin signaling via protein kinase C-induced serine phosphorylation of insulin receptor substrate-1. In the liver, FFAs cause insulin resistance by interfering with insulin suppression of glycogenolysis. In the beta cells, FFAs potentiate glucose-stimulated insulin secretion. It is postulated that this prevents the development type 2 diabetes mellitus in the majority (approximately 80%) of obese insulin-resistant people. SUMMARY: Elevated plasma FFA levels have been shown to account for up to 50% of insulin resistance in obese patients with type 2 diabetes mellitus. Lowering of FFAs in these patients or interfering with steps in the pathway through which FFAs cause insulin resistance could be a new and promising approach to treat type 2 diabetes mellitus. Publication Types: a.. Review b.. Review, Tutorial PMID: 12172479 [PubMed - indexed for MEDLINE]
– Hide quoted text — Show quoted text -> Okay, just beginning the research, but apparently with some > diabetics there is a whole host of problems the docs are > calling ‘metabolic syndrome’ which is about as definitive as > dawn phenomenon and irritates the helloutta me. > Here’s a link to full text articles about this issue (it’s > PDF and might take a while to upload) > http://www.nutrition.org/cgi/reprint/131/8/2078.pdf > http://edrv.endojournals.org/cgi/content/full/23/2/201 > Anyway, the following are abstracts from PubMed: — > Is hepatic glucose production increased in type 2 diabetes > mellitus? > Beck-Nielsen H, Hother-Nielsen O, Staehr P. > Department of Endocrinology M, Odense University Hospital, > Klovervaenget 6.4, DK-5000 Odense C, Denmark. > Based on recent studies, including our own, using what we > consider to be an appropriate technique to estimate rates of > hepatic glucose production (HGP), this article can be > summarized as follows: 1) HGP in the overnight fasted state > is near normal in obese type 2 diabetes (T2D) subjects, > i.e., it may be increased by a mean of 12% compared to > matched control subjects. 2) Suppression of HGP by insulin > shows a rightward shift of the dose response curve (reduced > insulin sensitivity) but normal maximal suppression (no > maximum velocity defect). 3) In the overnight fasted state, > gluconeogenesis is responsible for two thirds of HGP in T2D > subjects and is about 5% to 10% increased compared to > healthy subjects. 4) Suppression of HGP during a meal is > close to normal. 5) The slightly increased HGP values > throughout the 24-hour period together with reduced > metabolic clearance rate (peripheral insulin resistance) and > increased carbohydrate intake is responsible for the > increase in fasting plasma glucose values. 6) > Hypothetically, the role of the liver in nondiabetic and T2D > subjects may be to produce the amount of glucose needed for > metabolism in peripheral tissues. If insulin-mediated > glucose uptake in skeletal muscle is reduced, plasma glucose > will increase due to the "nonsuppressed" HGP values. Plasma > glucose continues to rise until glucose-mediated glucose > uptake compensates completely for the reduction in > insulin-mediated glucose uptake. > Publication Types: > a.. Review > b.. Review, Tutorial > PMID: 12643178 [PubMed - indexed for MEDLINE] — — > The liver in obesity and type 2 diabetes mellitus. > Li Z, Clark J, Diehl AM. > Division of Gastroenterology, Department of Medicine, Johns > Hopkins University School of Medicine, 912 Ross Research > Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. > Obesity and type 2 diabetes are associated strongly with > NAFLD. It is not clear if one of these conditions causes the > others, or if all are consequences of another process. > Although NAFLD is known to occur in overly lean individuals, > which indicates that excessive adiposity is not required for > the development of NAFLD, the severities of insulin > resistance and NAFLD tend to parallel each other, and the > greatest prevalence of type 2 diabetes occurs in patients > with NAFLD and cirrhosis. This observation suggests that > insulin resistance and NAFLD may be related pathogenically. > Experiments in mice demonstrate that insulin resistance and > NAFLD result from a chronic inflammatory state that is > characterized by increased levels of TNF alpha. The > mechanisms that drive this chronic inflammation are unknown > but might involve the oxidative stress that develops during > fatty acid metabolism or when products from intestinal > bacteria escape into the mesenteric blood to trigger a > sustained hepatic inflammatory cytokine response in > genetically susceptible individuals, promoting a positive > feedback loop that reinforces insulin resistance and > inflammation. This hypothesis is supported by some animal > and human studies; however, more research is needed to > evaluate this theory. Additional studies also are required > to determine the benefits of treatments that interrupt this > pathogenic cascade at various points. Preliminary work in > animal and human studies suggests that diverse strategies > that inhibit production of TNF alpha and improve insulin > resistance also ameliorate NAFLD. > Publication Types: > a.. Review > b.. Review, Tutorial > PMID: 12516196 [PubMed - indexed for MEDLINE] — > Hepatic steatosis and type 2 diabetes mellitus. > Clark JM, Diehl AM. > Department of Medicine, Johns Hopkins University School of > Medicine, 912 Ross Building, 720 Rutland Street, Baltimore, > MD 21205, USA. > Type 2 diabetes is strongly associated with nonalcoholic > fatty liver disease (NAFLD), a spectrum of liver damage that > ranges from relatively benign hepatic steatosis to > potentially fatal cirrhosis. The severities of insulin > resistance and liver damage parallel each other, with the > greatest prevalence of cirrhosis occurring in cirrhotics. > However, it is unknown whether one of these conditions > causes the other, or if both are consequences of another > process. Experimental evidence suggests that both insulin > resistance and NAFLD result from a chronic inflammatory > state. The mechanisms driving this chronic inflammation are > unknown but might include the egress of products from > intestinal bacteria into the portal blood, liver, and > systemic circulation to trigger a sustained inflammatory > cytokine response in genetically susceptible individuals. > More research is needed to evaluate this hypothesis and to > determine the benefits of treatments that interrupt this > pathogenic cascade. > Publication Types: > a.. Review > b.. Review, Tutorial > PMID: 12643175 [PubMed - indexed for MEDLINE] — > Adipose tissue and the insulin resistance syndrome. > Frayn KN. > Oxford Centre for Diabetes, Endocrinology and Metabolism, > Obesity is associated with insulin resistance. Insulin > resistance underlies a constellation of adverse metabolic > and physiological changes (the insulin resistance syndrome) > which is a strong risk factor for development of type 2 > diabetes and CHD. The present article discusses how > accumulation of triacylglycerol in adipocytes can lead to > deterioration of the responsiveness of glucose metabolism in > other tissues. Lipodystrophy, lack of adipose tissue, is > also associated with insulin resistance. Any plausible > explanation for the link between excess adipose tissue and > insulin resistance needs to be able to account for this > observation. Adipose tissue in obesity becomes refractory to > suppression of fat mobilization by insulin, and also to the > normal acute stimulatory effect of insulin on activation of > lipoprotein lipase (involved in fat storage). The net effect > is as though adipocytes are ‘full up’ and resisting further > fat storage. Thus, in the postprandial period especially, > there is an excess flux of circulating lipid metabolites > that would normally have been ‘absorbed’ by adipose tissue. > This situation leads to fat deposition in other tissues. > Accumulation of triacylglycerol in skeletal muscles and in > liver is associated with insulin resistance. In > lipodystrophy there is insufficient adipose tissue to absorb > the postprandial influx of fatty acids, so these fatty acids > will again be directed to other tissues. This view of the > link between adipose tissue and insulin resistance > emphasises the important role of adipose tissue in > ‘buffering’ the daily influx
… read more »
Response:
Here’s the link to the full text article with an abstract below: http://ajpendo.physiology.org/cgi/content/full/273/4/E708 Obesity is associated with both insulin resistance and hyperinsulinemia. Initially hyperinsulinemia compensates for the insulin resistance and thereby maintains normal glucose homeostasis. Obesity is also associated with increased tissue triglyceride (TG) content. To determine whether both insulin resistance and hyperinsulinemia might be secondary to increased tissue TG, we studied correlations between TG content of skeletal muscle, liver, and pancreas and plasma insulin, plasma [insulin]
Related Posts