Effects of fatty acids and ketone bodies on basal insulin secretion in type 2 diabetes

Diabetes ◽  
1999 ◽  
Vol 48 (3) ◽  
pp. 577-583 ◽  
Author(s):  
G. Boden ◽  
X. Chen
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Secretion ◽  
Basal Insulin ◽  
Ketone Bodies ◽  
Basal Insulin Secretion

scholarly journals Elevated Basal Insulin Secretion in Type 2 Diabetes Caused by Reduced Plasma Membrane Cholesterol

2016 ◽  
Vol 30 (10) ◽  
pp. 1059-1069 ◽  
Author(s):  
Vini Nagaraj ◽  
Abdulla S. Kazim ◽  
Johan Helgeson ◽  
Clemens Lewold ◽  
Satadal Barik ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Membrane ◽  
Insulin Secretion ◽  
Basal Insulin ◽  
Membrane Cholesterol ◽  
Basal Insulin Secretion ◽  
Plasma Membrane Cholesterol

scholarly journals Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 800
Author(s):  
Isabella D. Cooper ◽  
Kenneth H. Brookler ◽  
Yvoni Kyriakidou ◽  
Bradley T. Elliott ◽  
Catherine A. P. Crofts
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Basal Insulin ◽  
Uncoupling Protein ◽  
Primary Role ◽  
Metabolic Phenotypes ◽  
Insulin Levels ◽  
Basal Insulin Secretion ◽  
Beta Hydroxybutyrate

Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin’s primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.

Effect of fatty acids on insulin release: role of chain length and degree of unsaturation

1994 ◽  
Vol 266 (4) ◽  
pp. E635-E639 ◽  
Author(s):  
E. C. Opara ◽  
M. Garfinkel ◽  
V. S. Hubbard ◽  
W. M. Burch ◽  
O. E. Akwari
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Basal Insulin ◽  
Degree Of Unsaturation ◽  
Structural Differences ◽  
Basal Insulin Secretion

The purpose of the present study was to examine the role played by structural differences among fatty acids in their effect on insulin secretion by isolated perifused murine islets. Insulin secretion measured by radioimmunoassay was assessed either as total insulin output (ng.6 islets-1.20 min-1) or as percent of basal insulin secretion. Raising the glucose concentration from a basal 5.5 to 27.7 mM caused an increase of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng.6 islets-1.20 min-1 (P < 0.05) in control (untreated) islets. However, after 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin output (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the addition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. Insulin output increased modestly with 5 mM 8:0 but significantly (P < 0.05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.01), then fell to 110 +/- 18 and 93 +/- 15% basal (P < 0.05) with 14:0 and 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin secretion to 30 +/- 10% of basal (P < 0.003), and this effect was not caused by fatty acid interference with insulin assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute lowering of circulating fatty acids improves insulin secretion in a subset of type 2 diabetes subjects

2003 ◽  
Vol 284 (1) ◽  
pp. E129-E137 ◽  
Author(s):  
Elisabeth Qvigstad ◽  
Ingrid L. Mostad ◽  
Kristian S. Bjerve ◽  
Valdemar E. Grill
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Secretion ◽  
Dietary Intervention ◽  
Insulin Response ◽  
Low Fat Diet ◽  
Hyperglycemic Clamp ◽  
Glucose Stimulated Insulin Secretion ◽  
Secretion Rates

We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type 2 diabetes. Twenty-one type 2 diabetes subjects with hypertriglyceridemia (triacylglycerol >2.2 mmol/l) and 10 age-matched nondiabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during minutes 60–120. In one of two tests, the subjects ingested 250 mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in 17 of the diabetic subjects after 3 days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in nondiabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in nondiabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects, Acipimox increased integrated insulin secretion rates during minutes 60–120 in the 50% having the lowest levels of hemoglobin A1c (379 ± 34 vs. 326 ± 30 pmol · kg−1 · min−1without Acipimox, P < 0.05). A 3-day dietary intervention diminished energy from fat from 39 to 23% without affecting FA levels and without improving the insulin response during clamps. Elevated FA levels may tonically inhibit stimulated insulin secretion in a subset of type 2 diabetic subjects.

scholarly journals Short Course of Insulin Treatment versus Metformin in Newly Diagnosed Patients with Type 2 Diabetes

2018 ◽  
Vol 7 (9) ◽  
pp. 235 ◽  
Author(s):  
Marta Seghieri ◽  
Eleni Rebelos ◽  
Andrea Mari ◽  
Luigi Sciangula ◽  
Carlo Giorda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Basal Insulin ◽  
Insulin Treatment ◽  
Oral Glucose ◽  
Newly Diagnosed ◽  
Insulin Group ◽  
Short Course

The ß-cell dysfunction of type 2 diabetes is partly reversible. The optimal time window to induce glycemic remission is uncertain; short courses of insulin treatment have been tested as a strategy to induce remission. In a pilot study in 38 newly-diagnosed patients, we assessed the time-course of insulin sensitivity and ß-cell function (by repeat oral glucose tolerance tests) following a 6-week basal insulin treatment compared to metformin monotherapy in equipoised glycemic control. At 6 weeks, insulin secretion and sensitivity were increased in both groups whilst ß-cell glucose sensitivity was unchanged. From this time onwards, in the insulin group glycemia started to rise at 3 months, and was no longer different from baseline at 1 year. The initial improvement in insulin secretion and sensitivity dissipated. In the metformin group, fasting plasma glucose and HbA1c levels reached a nadir at 8 months, at which time insulin secretion, glucose and insulin sensitivity were significantly better than at baseline and higher than in the insulin group. A short course of basal insulin in newly-diagnosed patients does not appear to offer clinical advantage over recommended initiation with metformin.

scholarly journals Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion

2021 ◽  
Vol 23 (1) ◽  
pp. 324
Author(s):  
Lucie Oberhauser ◽  
Pierre Maechler
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Secretion ◽  
Free Fatty Acids ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Accelerated Aging ◽  
Β Cell

Over the last decades, lipotoxicity and glucotoxicity emerged as established mechanisms participating in the pathophysiology of obesity-related type 2 diabetes in general, and in the loss of β-cell function in particular. However, these terms hold various potential biological processes, and it is not clear what precisely they refer to and to what extent they might be clinically relevant. In this review, we discuss the basis and the last advances of research regarding the role of free fatty acids, their metabolic intracellular pathways, and receptor-mediated signaling related to glucose-stimulated insulin secretion, as well as lipid-induced β-cell dysfunction. We also describe the role of chronically elevated glucose, namely, glucotoxicity, which promotes failure and dedifferentiation of the β cell. Glucolipotoxicity combines deleterious effects of exposures to both high glucose and free fatty acids, supposedly provoking synergistic defects on the β cell. Nevertheless, recent studies have highlighted the glycerolipid/free fatty acid cycle as a protective pathway mediating active storage and recruitment of lipids. Finally, we discuss the putative correspondence of the loss of functional β cells in type 2 diabetes with a natural, although accelerated, aging process.

scholarly journals Glucolipotoxicity of the pancreatic β-cell: myth or reality?

2008 ◽  
Vol 36 (5) ◽  
pp. 901-904 ◽  
Author(s):  
Vincent Poitout
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Secretion ◽  
Insulin Gene ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
In Vitro Systems ◽  
Insulin Gene Expression

The glucolipotoxicity hypothesis postulates that chronically elevated levels of glucose and fatty acids adversely affect pancreatic β-cell function and thereby contribute to the deterioration of insulin secretion in Type 2 diabetes. Whereas ample experimental evidence in in vitro systems supports the glucolipotoxicity hypothesis, the contribution of this phenomenon to β-cell dysfunction in human Type 2 diabetes has been questioned. The reasons for this controversy include: differences between in vitro systems and in vivo situations; time-dependent effects of fatty acids on insulin secretion (acutely stimulatory and chronically inhibitory); and the ill-defined use of the suffix ‘-toxicity’. In vitro, prolonged exposure of insulin-secreting cells or isolated islets to concomitantly elevated levels of fatty acids and glucose impairs insulin secretion, inhibits insulin gene expression and, under certain circumstances, induces β-cell death by apoptosis. Recent studies in our laboratory have shown that cyclical and alternate infusions of glucose and Intralipid in rats impair insulin gene expression, providing evidence that inhibition of the insulin gene under glucolipotoxic conditions is an early defect that might indeed contribute to β-cell failure in Type 2 diabetes, although this hypothesis remains to be tested in humans.

Sign in / Sign up

Export Citation Format

Share Document