Pattern of Postprandial Carbohydrate Metabolism and Effects of Portal and Peripheral Insulin Delivery

Kryshak, Edward J.; Butler, Peter C.; Marsh, Christopher L.; Miller, Anthony; Barr, Darlene; Polonsky, Kenneth S.; Perkins, James D.; Rizza, Robert A.

doi:10.2337/diab.39.2.142

Cited by 30 publications

(1 citation statement)

References 44 publications

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“…Hence, 2 at high concentration had an additional impact on pancreatic function in obesity-induced insulin resistance that was absent at lower levels of this compound and/or when 2 acts in combination with other phytochemicals present in the unaltered PMI-5011 extract. Conversely, C-peptide levels were unchanged by KOE, raising the possibility that the increased insulin levels with KOE reflect a modulating impact of methyldavidigenins on hepatic and extrahepatic insulin clearance. − …”

Section: Resultsmentioning

confidence: 99%

The DESIGNER Approach Helps Decipher the Hypoglycemic Bioactive Principles of Artemisia dracunculus (Russian Tarragon)

Simmler

Kühn

et al. 2019

J. Nat. Prod.

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Complementing classical drug discovery, phytochemicals act on multiple pharmacological targets, especially in botanical extracts, where they form complex bioactive mixtures. The reductionist approach used in bioactivity-guided fractionation to identify single bioactive phytochemicals is inadequate for capturing the full therapeutic potential of the (bio)chemical interactions present in such complex mixtures. This study used a DESIGNER (Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources) approach to selectively remove the known bioactives, 4′-O-methyldavidigenin (1; 4,2′-dihydroxy-4′-methoxydihydrochalcone, syn. DMC-1) and its isomer 4-O-methyldavidigenin (2; syn. DMC-2), from the mixture of phytochemicals in an ethanol extract from Artemisia dracunculus to determine to what degree the more abundant 2 accounts for the established antidiabetic effect of the A. dracunculus extract. Using an otherwise chemically intact “knock-out extract” depleted in 2 and its regioisomer, 1, in vitro and in vivo outcomes confirmed that 2 (and likely 1) acts as major bioactive(s) that enhance(s) insulin signaling in skeletal muscle, but also revealed that 2 does not account for the breadth of detectable biological activity of the extract. This is the first report of generating, at a sufficiently large preparative scale, a “knock-out extract” used as a pharmacological tool for in vitro and in vivo studies to dissect the biological impact of a designated bioactive in a complex phytochemical mixture.

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Section: Resultsmentioning

confidence: 99%

The DESIGNER Approach Helps Decipher the Hypoglycemic Bioactive Principles of Artemisia dracunculus (Russian Tarragon)

Simmler

Kühn

et al. 2019

J. Nat. Prod.

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Implantable Pumps

Saudek

Chia

2003

International Textbook of Diabetes Mellitus

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Implantable insulin pumps (IIPs) have been under development for a number of years now, with a variable rate, externally programmable IIPs now having been used for as long as 15 years. The major obstacles in its development, including an insulin manufacturing change that caused increased aggregation and some pump module adjustments, have been largely overcome. Medtronic MiniMed Corp. is the sole manufacturer at present developing the implanted pump, and is using a new model that features a battery life expectancy of 8 years and a smaller, faster external programmer. The majority of implanted insulin pump experience has been accrued in France, where excellent data on safety and efficacy have been gathered. A randomized clinical trial conducted in US Veterans Affairs Medical Centers demonstrated that compared with multiple‐dose insulin regimens, implanted insulin pumps caused less hypoglycemia, less weight gain, and improved quality of life.

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Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis

1991

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Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 +/- 0.1 mg/kg/min vs. 8.1 +/- 0.5 mg/kg/min; p less than 0.001), which also demonstrated a low insulin metabolic clearance rate (p less than 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 +/- 1.0 mg/kg/min; controls: 6.3 +/- 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance. C-peptide MCR was identical in cirrhotic patients (2.93 +/- 0.16 ml/min/kg) and controls (2.96 +/- 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 +/- 0.26 U/hr vs. 1.09 +/- 0.10 U/hr; p less than 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 +/- 0.70 U/hr vs. 2.85 +/- 0.22 U/hr; p less than 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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Pattern of Postprandial Carbohydrate Metabolism and Effects of Portal and Peripheral Insulin Delivery

Cited by 30 publications

References 44 publications

The DESIGNER Approach Helps Decipher the Hypoglycemic Bioactive Principles of Artemisia dracunculus (Russian Tarragon)

The DESIGNER Approach Helps Decipher the Hypoglycemic Bioactive Principles of Artemisia dracunculus (Russian Tarragon)

Implantable Pumps

Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis

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