Lipids and Glucose in Type 2 Diabetes

Boden, Guenther; Laakso, Markku

doi:10.2337/diacare.27.9.2253

Cited by 152 publications

(119 citation statements)

References 91 publications

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“…These characteristics are similar to the human diabetic condition, and it may be that the pathology of diabetes in humans is adaptive in a species that fasts for long durations and exists on a diet high in lipid and protein but devoid of carbohydrate. Short-term elevations of plasma NEFA have been shown to induce hepatic and peripheral insulin resistance and possibly increase EGP (6,26,27). Conversely, under constant circulating concentrations of insulin, glucagon, and cortisol, hyperglycemia (200% basal levels) has been demonstrated to reduce rates of lipolysis by up to 30% (13).…”

Section: Discussionmentioning

confidence: 99%

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Houser¹,

Champagne²,

Crocker³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Adult female elephant seals (Mirounga angustirostris) combine long-term fasting with lactation and molting. Glycerol gluconeogenesis has been hypothesized as potentially meeting all of the glucose requirements of the seals during these fasts. To test this hypothesis, a primed constant infusion of [2-14 C]glycerol was administered to 10 ten adult female elephant seals at 5 and 21-22 days postpartum and to 10 additional adult females immediately after the molt. Glycerol kinetics, rates of lipolysis, and the contribution of glycerol to glucose production were determined for each period. Plasma metabolite levels as well as insulin, glucagon, and cortisol were also measured. Glycerol rate of appearance was not significantly correlated with mass (P ϭ 0.14, r 2 ϭ 0.33) but was significantly related to the percentage of glucose derived from glycerol (P Ͻ 0.01, r 2 ϭ 0.81) during late lactation. The contribution of glycerol to glucose production was Ͻ3% during each fasting period, suggesting a lower contribution to gluconeogenesis than is observed in other long-term fasting mammals. Because of a high rate of endogenous glucose production in fasting elephant seals, it is likely that glycerol gluconeogenesis still makes a substantial contribution to the substrate needs of glucose-dependent tissues. The lack of a relationship between glucoregulatory hormones and glycerol kinetics, glycerol gluconeogenesis, and metabolites supports the proposition that fasting elephant seals do not conform to the traditional insulinglucagon model of substrate metabolism. reesterification; lipid metabolism; lactogenesis; glucagon; insulin GLUCONEOGENESIS IS an important physiological process in maintaining blood glucose levels during fasting and can meet Ͼ90% of glucose needs after just 2 days of fasting (28). Both amino acids and glycerol can be metabolized to glucose when exogenous carbohydrate becomes unavailable. However, under long-term fasting conditions the loss of protein is generally minimized to stay the eventual loss of organ function that results from protein depletion. Under these conditions glycerol becomes an increasingly important gluconeogenic precursor. In the postabsorptive state, the conversion of glycerol to glucose accounts for ϳ3-4.5% of glucose production; however, after fasting for several days, the contribution of glycerol to glucose production increases to ϳ10 -22% (2, 7, 29). After weeks of fasting glycerol can contribute up to 60% of glucose production (7), although the basis for this calculation has come into question because of methodological issues related to the separation of radiolabeled glycerol from radiolabeled glucose (2). Thus, during long-duration fasts, the availability of lipid stores not only serves to provide energy via fatty acid oxidation but also contributes to meeting the energetic costs of glucose-dependent tissues.Northern elephant seals (Mirounga angustirostris) undertake prolonged fasts of 1-3 mo. Adult females undertake two fasts each year, one while lactating and another while molting. Bot...

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Section: Discussionmentioning

confidence: 99%

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Houser¹,

Champagne²,

Crocker³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…What could be the mechanisms via which acarbose modifies the effect of SNPs of PPARD and PGC-1A on the risk of diabetes? Postprandial hyperglycemia and high FFAs contribute to the production of reactive oxygen species (16,21), which increase mitochondrial mass, mainly by overexpression of nuclear respiratory factors and PGC-1␣ (22). Both acarbose and PGC-1␣ have a protective effect on reactive oxygen species formation, either by alleviating postprandial hyperglycemia and high FFAs or by transcriptionally regulating the mitochondrial antioxidant defense system (23).…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphisms of PPARD in Combination With the Gly482Ser Substitution of PGC-1A and the Pro12Ala Substitution of PPARG2 Predict the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

et al. 2006

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“…Abnormalities in lipid metabolism, particularly overabundance of circulating NEFA, have been shown to play an important role in this process (for review, see [22,23]). …”

Section: Discussionmentioning

confidence: 99%

“…In the postprandial phase, TGRL lipolysis occurs predominantly in the adipose tissue capillaries with NEFA uptake by adipose tissue, however, being incomplete; between 20 and 80% of NEFA escape adipose tissue entrapment [19] to be taken up by liver and muscle [20,21], both major sites of insulin resistance. For these two tissues, numerous human and animal studies have shown that elevated plasma NEFA levels induce insulin resistance (for review see [22,23]). The other two lipid components involved in the lipolytic process, i.e.…”

Section: Introductionmentioning

confidence: 99%

Postprandial lipaemia induces an acute decrease of insulin sensitivity in healthy men independently of plasma NEFA levels

et al. 2006

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Aims/hypothesis: Typical Western diets cause postprandial lipaemia for 18 h per day. We tested the hypothesis that postprandial lipaemia decreases insulin sensitivity. Subjects, materials and methods: Employing a randomised crossover design, we administered two types of virtually isocaloric meals to ten healthy volunteers on two separate occasions. The meals (Meals 1 and 2) were both designed to produce a rise in triglycerides, but only Meal 1 generated a rise in NEFA, too. Insulin sensitivity, as quantified by an IVGTT with minimal model analysis, was calculated postabsorptively at 08.00 h and postprandially at 13.00 h, i.e. 3 h after meal ingestion. Results: Triglycerides rose from 0.91±0.31 mmol/l postabsorptively to 2.08±0.70 mmol/l postprandially with Meal 1 (p=0.005) and from 0.92±0.41 to 1.71±0.79 mmol/ l with Meal 2 (p=0.005). Neither the triglyceride levels at 13.00 h, nor the post-meal AUCs for triglycerides were statistically different between Meal 1 and Meal 2. NEFA rose from 0.44±0.17 mmol/l postabsorptively to 0.69±0.16 mmol/ l postprandially with Meal 1 (p=0.005) and showed no significant change with Meal 2 (0.46±0.31 mmol/l postabsorptively vs 0.36±0.32 mmol/l postprandially, p=0.09). Both the NEFA level at 13.00 h and the post-meal AUC for NEFA were significantly higher after Meal 1 than Meal 2. Compared with the postabsorptive state, insulin sensitivity decreased postprandially after each of the two meals to a comparable degree (Meal 1: −53%, p=0.02; Meal 2: −45%, p=0.005). Conclusions/interpretation: Our study reveals a drop in insulin sensitivity during postprandial lipaemia and strongly suggests that decreased insulin sensitivity is brought about by elevated plasma levels of triglyceride-rich lipoproteins independently of plasma NEFA levels.

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Lipids and Glucose in Type 2 Diabetes

Cited by 152 publications

References 91 publications

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Single Nucleotide Polymorphisms of PPARD in Combination With the Gly482Ser Substitution of PGC-1A and the Pro12Ala Substitution of PPARG2 Predict the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

Postprandial lipaemia induces an acute decrease of insulin sensitivity in healthy men independently of plasma NEFA levels

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